JP7374634B2 - レチノイドの副作用に対する感受性の決定方法 - Google Patents
レチノイドの副作用に対する感受性の決定方法 Download PDFInfo
- Publication number
- JP7374634B2 JP7374634B2 JP2019130064A JP2019130064A JP7374634B2 JP 7374634 B2 JP7374634 B2 JP 7374634B2 JP 2019130064 A JP2019130064 A JP 2019130064A JP 2019130064 A JP2019130064 A JP 2019130064A JP 7374634 B2 JP7374634 B2 JP 7374634B2
- Authority
- JP
- Japan
- Prior art keywords
- side effects
- retinoid
- susceptibility
- sensitivity
- retinoids
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000000694 effects Effects 0.000 title claims description 72
- 150000004492 retinoid derivatives Chemical class 0.000 title claims description 46
- 206010071602 Genetic polymorphism Diseases 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 53
- 108090000623 proteins and genes Proteins 0.000 claims description 48
- 230000035945 sensitivity Effects 0.000 claims description 45
- 239000003814 drug Substances 0.000 claims description 33
- 229940079593 drug Drugs 0.000 claims description 29
- 102000004169 proteins and genes Human genes 0.000 claims description 21
- 102100021196 Glypican-5 Human genes 0.000 claims description 17
- 101001040711 Homo sapiens Glypican-5 Proteins 0.000 claims description 17
- 239000002537 cosmetic Substances 0.000 claims description 17
- 230000014509 gene expression Effects 0.000 claims description 16
- 230000009471 action Effects 0.000 claims description 15
- 101000666074 Homo sapiens WD repeat-containing protein 7 Proteins 0.000 claims description 14
- 102100038088 WD repeat-containing protein 7 Human genes 0.000 claims description 13
- 230000008859 change Effects 0.000 claims description 13
- 101000983518 Homo sapiens Caspase-10 Proteins 0.000 claims description 12
- 101001091194 Homo sapiens Peptidyl-prolyl cis-trans isomerase G Proteins 0.000 claims description 12
- 102100021198 Chemerin-like receptor 2 Human genes 0.000 claims description 11
- 101000750094 Homo sapiens Chemerin-like receptor 2 Proteins 0.000 claims description 11
- 102100035768 Calcyphosin-like protein Human genes 0.000 claims description 10
- 101000715551 Homo sapiens Calcyphosin-like protein Proteins 0.000 claims description 10
- 101000866308 Homo sapiens Excitatory amino acid transporter 4 Proteins 0.000 claims description 10
- 102000012985 SLC1A6 Human genes 0.000 claims description 10
- 238000012216 screening Methods 0.000 claims description 10
- 102100021277 Beta-secretase 2 Human genes 0.000 claims description 7
- 101000894883 Homo sapiens Beta-secretase 2 Proteins 0.000 claims description 7
- 101000668168 Homo sapiens RNA-binding motif, single-stranded-interacting protein 3 Proteins 0.000 claims description 5
- 102100039689 RNA-binding motif, single-stranded-interacting protein 3 Human genes 0.000 claims description 5
- 210000004748 cultured cell Anatomy 0.000 claims description 3
- 102100026549 Caspase-10 Human genes 0.000 claims 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 40
- 210000003491 skin Anatomy 0.000 description 23
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 22
- 229960003471 retinol Drugs 0.000 description 18
- 235000020944 retinol Nutrition 0.000 description 18
- 239000011607 retinol Substances 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 17
- -1 AC005009.1 Proteins 0.000 description 10
- 102100034850 Peptidyl-prolyl cis-trans isomerase G Human genes 0.000 description 9
- 230000003796 beauty Effects 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 7
- 102000039446 nucleic acids Human genes 0.000 description 7
- 150000007523 nucleic acids Chemical class 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 229960001727 tretinoin Drugs 0.000 description 7
- 102100022715 Acetyl-coenzyme A thioesterase Human genes 0.000 description 6
- 101000678862 Homo sapiens Acetyl-coenzyme A thioesterase Proteins 0.000 description 6
- 101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000007477 logistic regression Methods 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 229930002330 retinoic acid Natural products 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 206010015150 Erythema Diseases 0.000 description 4
- 102100035108 High affinity nerve growth factor receptor Human genes 0.000 description 4
- 101000596894 Homo sapiens High affinity nerve growth factor receptor Proteins 0.000 description 4
- 101000834937 Homo sapiens Tomoregulin-1 Proteins 0.000 description 4
- 108010067244 Origin Recognition Complex Proteins 0.000 description 4
- 102000016304 Origin Recognition Complex Human genes 0.000 description 4
- 102100026159 Tomoregulin-1 Human genes 0.000 description 4
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000004807 localization Effects 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 238000003068 pathway analysis Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 235000019155 vitamin A Nutrition 0.000 description 4
- 239000011719 vitamin A Substances 0.000 description 4
- 229940045997 vitamin a Drugs 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 3
- 238000012098 association analyses Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000009223 counseling Methods 0.000 description 3
- 239000002853 nucleic acid probe Substances 0.000 description 3
- 230000019612 pigmentation Effects 0.000 description 3
- 230000002207 retinal effect Effects 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- 210000000434 stratum corneum Anatomy 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 101150035233 Cabp5 gene Proteins 0.000 description 2
- 102100023243 Calcium-activated potassium channel subunit beta-3 Human genes 0.000 description 2
- 102100030051 Calcium-binding protein 5 Human genes 0.000 description 2
- 102100024911 Caveolae-associated protein 4 Human genes 0.000 description 2
- 102100040626 Cytosolic phospholipase A2 gamma Human genes 0.000 description 2
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 2
- 239000003298 DNA probe Substances 0.000 description 2
- 102100028147 F-box/WD repeat-containing protein 4 Human genes 0.000 description 2
- 102100035924 Gamma-aminobutyric acid type B receptor subunit 2 Human genes 0.000 description 2
- 101001049845 Homo sapiens Calcium-activated potassium channel subunit beta-2 Proteins 0.000 description 2
- 101001049846 Homo sapiens Calcium-activated potassium channel subunit beta-3 Proteins 0.000 description 2
- 101000761524 Homo sapiens Caveolae-associated protein 4 Proteins 0.000 description 2
- 101000614106 Homo sapiens Cytosolic phospholipase A2 gamma Proteins 0.000 description 2
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 2
- 101001060244 Homo sapiens F-box/WD repeat-containing protein 4 Proteins 0.000 description 2
- 101001000703 Homo sapiens Gamma-aminobutyric acid type B receptor subunit 2 Proteins 0.000 description 2
- 101001063878 Homo sapiens Leukemia-associated protein 1 Proteins 0.000 description 2
- 101000742901 Homo sapiens Lysophosphatidylserine lipase ABHD12 Proteins 0.000 description 2
- 101001032848 Homo sapiens Metabotropic glutamate receptor 3 Proteins 0.000 description 2
- 101000601056 Homo sapiens NIF3-like protein 1 Proteins 0.000 description 2
- 101001084266 Homo sapiens Parathyroid hormone 2 receptor Proteins 0.000 description 2
- 101000805129 Homo sapiens Protein DPCD Proteins 0.000 description 2
- 101000911547 Homo sapiens Protein FAM214B Proteins 0.000 description 2
- 101000979284 Homo sapiens Protein kinase C-binding protein NELL1 Proteins 0.000 description 2
- 101000732374 Homo sapiens Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B Proteins 0.000 description 2
- 101001026232 Homo sapiens Small conductance calcium-activated potassium channel protein 3 Proteins 0.000 description 2
- 101000831927 Homo sapiens Stomatin-like protein 2, mitochondrial Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 101000756787 Homo sapiens Transcription factor RFX3 Proteins 0.000 description 2
- 208000008017 Hypohidrosis Diseases 0.000 description 2
- 102100030893 Leukemia-associated protein 1 Human genes 0.000 description 2
- 102100038056 Lysophosphatidylserine lipase ABHD12 Human genes 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 2
- 102100037380 NIF3-like protein 1 Human genes 0.000 description 2
- 102100030869 Parathyroid hormone 2 receptor Human genes 0.000 description 2
- 102100037836 Protein DPCD Human genes 0.000 description 2
- 102100026954 Protein FAM214B Human genes 0.000 description 2
- 102100023068 Protein kinase C-binding protein NELL1 Human genes 0.000 description 2
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 2
- 108091006280 SLC5A11 Proteins 0.000 description 2
- 102100033329 Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B Human genes 0.000 description 2
- 102100037442 Small conductance calcium-activated potassium channel protein 3 Human genes 0.000 description 2
- 102100037202 Sodium/myo-inositol cotransporter 2 Human genes 0.000 description 2
- 102100024172 Stomatin-like protein 2, mitochondrial Human genes 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 102100022821 Transcription factor RFX3 Human genes 0.000 description 2
- 239000012445 acidic reagent Substances 0.000 description 2
- 229930002945 all-trans-retinaldehyde Natural products 0.000 description 2
- 206010002512 anhidrosis Diseases 0.000 description 2
- 230000037001 anhydrosis Effects 0.000 description 2
- 230000001153 anti-wrinkle effect Effects 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 238000004299 exfoliation Methods 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 210000000887 face Anatomy 0.000 description 2
- 238000003205 genotyping method Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- NCYCYZXNIZJOKI-OVSJKPMPSA-N retinal group Chemical group C\C(=C/C=O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 230000035909 sensory irritation Effects 0.000 description 2
- 230000005808 skin problem Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 2
- 230000002087 whitening effect Effects 0.000 description 2
- BYJQAPYDPPKJGH-UHFFFAOYSA-N 3-(2-carboxyethyl)-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2C(CCC(=O)O)=C(C(O)=O)NC2=C1 BYJQAPYDPPKJGH-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
- 102100025351 C-type mannose receptor 2 Human genes 0.000 description 1
- 101150025087 CASP10 gene Proteins 0.000 description 1
- 101150083671 Capsl gene Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 208000019028 Epidermal thickening Diseases 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 101150041444 GPC5 gene Proteins 0.000 description 1
- 101150089139 GPR1 gene Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 101000576898 Homo sapiens C-type mannose receptor 2 Proteins 0.000 description 1
- 101100176251 Homo sapiens GPC5 gene Proteins 0.000 description 1
- 101000610557 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp31 Proteins 0.000 description 1
- 101000760224 Homo sapiens Zinc finger protein 337 Proteins 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- 241001262617 Japonica Species 0.000 description 1
- 101150111783 NTRK1 gene Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 101001109965 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L7-A Proteins 0.000 description 1
- 101001109960 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L7-B Proteins 0.000 description 1
- 208000020764 Sensation disease Diseases 0.000 description 1
- 101150045248 Slc1a6 gene Proteins 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- 102100040118 U4/U6 small nuclear ribonucleoprotein Prp31 Human genes 0.000 description 1
- 102100024659 Zinc finger protein 337 Human genes 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 229960001445 alitretinoin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 210000004177 elastic tissue Anatomy 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 230000036566 epidermal hyperplasia Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000001821 nucleic acid purification Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012175 pyrosequencing Methods 0.000 description 1
- 230000012279 response to vitamin A Effects 0.000 description 1
- 108090000064 retinoic acid receptors Proteins 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- WWDMJSSVVPXVSV-YCNIQYBTSA-N retinyl ester Chemical compound CC1CCCC(C)(C)C1\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O WWDMJSSVVPXVSV-YCNIQYBTSA-N 0.000 description 1
- 229940108325 retinyl palmitate Drugs 0.000 description 1
- 235000019172 retinyl palmitate Nutrition 0.000 description 1
- 239000011769 retinyl palmitate Substances 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 101150061587 rpsS gene Proteins 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Description
rs11264256、rs12129712、rs79393875、rs77098893、rs117172861、rs189364622、rs142413201、rs16836262、rs10190756、rs143833788、rs367757001、rs146490521、rs149747233、rs142834469、rs35219727、rs180936202、rs192883707、rs74384211、chr3:145318006:T:C、rs150321408、rs188646953、、rs6451234、rs12153578、rs12522083、rs2504905、rs6924827、rs75473584、rs1874404、rs75979900、rs74756212、chr7:57761277:GA:G、rs376694855、rs190896232、chr7:62622355:ATATATATATATATATATATATATATATATATATATATATATT:A、rs141378112、rs148217145、rs118097902、rs144455233、rs80110077、rs77590716、rs182345837、rs182712478、rs148109217、rs114276193、rs76234757、rs150594929、rs583641、rs568982、rs151336244、rs74341477、rs74712856、rs76086616、rs72213476、rs199680407、rs140189230、chr12:13295924:ACTT:A、rs5803510、rs117870315、rs139534747、rs112399579、rs72641020、rs72641025、rs139806172、rs72641051、rs72641054、rs146458360、rs17267348、rs17188613、rs72641063、chr13:93364715:AAC:A、rs16947848、rs1933192、rs17267362、rs17267369、rs1933191、rs117349244、rs56865501、rs141950809、rs72641088、rs67937794、rs66904991、rs66498781、rs57888578、rs60005783、rs11838810、rs11838825、rs11839660、rs11840951、rs72641100、rs67037212、rs78226726、rs34407653、rs57660170、rs7994061、rs78510371、rs17267439、rs11291152、rs7325627、rs9589649、rs9523866、rs71815886、rs1932194、rs17188760、rs4924269、rs57779669、rs11631905、rs146603798、rs76981822、rs34365165、rs1862450、rs56124193、rs142249518、rs75365663、rs12609658、rs76798890、rs12610503、rs10417947、rs113242419、rs10423303、rs8112254、rs186658317、chr20:25335351:G:A、chr20:25362934:T:C、chr20:25699935:T:G、rs2837971、rs9981747、rs73366468、rs3215895、rs61084367、rs59874887、rs58795078、rs77353301、rs72751553、rs72751555、rs114562381、rs4667864、rs12692666、rs10207946、chr2:167027058:A:G、rs117922874、rs200162964、chr3:176034566:A:G、rs2303137、rs1010600、rs7381111、rs10077384、rs142644927、rs147831886、rs4484457、rs147835552、rs7735423、rs1820005、rs12332211、rs4362916、rs4386714、rs6881783、rs199982719、rs17155553、rs7731680、rs6596535、rs6596536、rs10058377、rs17155559、rs7734977、rs7701241、rs10479259、rs10062431、rs73195737、rs59531312、rs10054393、rs189936937、chr8:64870523:AT:A、rs56290508、rs56354846、rs16919204、rs71471143、rs72837632、rs2175925、rs148267634、rs12772593、rs11595562、rs72260862、rs71940964、rs11596080、rs7923098、rs11816602、rs17105050、rs34638006、rs10887463、rs10887464、rs7093187、rs7075763、rs7086187、rs11201523、rs883802、rs142939963、rs10887465、rs7074418、rs200756077、chr10:87020520:A:AG、chr10:87020524:AAAATG:A、rs12359344、rs11201526、rs11201527、rs11201528、rs34168904、rs35164626、rs7098463、rs11492856、rs7092376、rs12763173、rs12764075、rs11511546、rs28766011、rs11201537、rs36071582、rs2882516、rs10509517、rs12769551、rs11368758、rs7910468、rs12775803、rs66483968、rs11201552、rs11201553、rs7920425、chr10:87112822:GA:G、rs71471155、rs9663303、rs72840999、rs72841000、rs11025696、rs11025697、rs11517566、rs12789625、rs151088833、rs11025698、rs11025699、rs35230659、rs34391252、rs150667993、rs75905889、rs193002524、chr11:21747092:GTGTTTGTGTGTT:G、rs35565978、rs61556663、rs74030727、rs11073552、rs148027820、rs142595348、rs144638318、rs147470668、rs3851135、rs62129325、rs144365368、rs3988408、rs11437257、rs141791163、rs10008137、rs7832052、rs7845083、chr11:95462296:C:CAT、及びrs9978357からなる群から選ばれる、少なくとも1の遺伝子多型を検出する工程、
検出された遺伝子多型に基づき、レチノイドの副作用に対する感受性を決定する工程
を含む、レチノイドの副作用に対する感受性の決定方法に関する。
候補薬剤を適用する工程、
適用された細胞において、下記の:ABHD12、AC005009.1,GRM3、AC005037.3,ORC2、AC067959.1,AC011752.1、AC068490.2、AC073218.2-AC012593.1、AC091487.1-RP11-181F12.1、ACSS1-VSX1、BACE2、BACE2-FAM3B、CABP5、CAPSL、CASP10、CD28,CD28-KRT18P39、CTD-2019O4.1-ANO5、CTD-2021J15.1-ACTG1P13、CTD-3194G12.1,CTB-75G16.3-CTD-3194G12.1、CTLA4、DLEU1、DPCD、FAM214B,STOML2、FBXW4、GABBR2、GPC5、GPC5,GPC5-AS1、GPC5-AS1,GPC5、GPC5-LINC00363、KCNN3、KIAA1467-EMP1、KRT18P39,AC125238.1,NPM1P33,KRT18P39-NPM1P33、LINC00364-BCRP9、MRPL50P1-AC009414.1、NIF3L1,ORC2,NIF3L1-ORC2,.、PTH2R、RBMS3、RFX3、RNU6-1060P-RP11-439H9.1、RNU6-446P,MRC2、RNU6-474P-CTLA4、RNU7-157P-MIR3147、RP11-125M16.1-PHACTR1、RP11-1324A7.2,ZNF716-RP11-1324A7.2、RP11-196D18.5-snoU2_19、RP11-196I18.4-RP11-417L14.1,.、RP11-347L18.1-RP11-300M24.1、RP1-135L22.1-RP11-204E9.1、RP11-368M16.7-RP11-548K12.6、RP11-373D7.1,snoU2_19-RP11-373D7.1、RP11-373D7.1-PHKG1P1、RP11-377D9.3、RP11-385J1.2,KCNMB2、RP11-500M10.1-AC091320.2、RP11-533K11.1-RP11-500M10.1、RP11-548K12.6,RP11-548K12.8,RP11-548K12.5,RP11-548K12.7、RP11-556I14.2、RP11-556I14.2,RP11-556I14.1、RP11-622L21.1-GM2AP1、RP11-702B10.1-ETS1、RP11-79C6.1,RP11-79C6.1-CAPSL、RPL4P5-RP11-366I21.1、SLC1A6、SLC5A11,TNRC6A-SLC5A11、SPRED1-FAM98B、WDR7-OT1,WDR7、ZNF337-VN1R108P、AC010127.3、ACOT12、ACOT12,ACOT12、AL592063.1-RP11-323I1.1、CTD-2147F2.1,CTD-2147F2.2、CTD-2147F2.1-RNA5SP401、CTD-2147F2.2,CTD-2147F2.1、GPR1、KCNH7-RPL7P61、MSANTD3-TMEFF1,TMEFF1、MURC,MSANTD3-TMEFF1,TMEFF1、NELL1、NELL1-CTD-2019O4.1、NUDT12-RP11-138J23.1、PERP-KIAA1244、PLA2G4C、RP11-181F12.1-RP11-475D12.1、RP11-32K4.1、RP11-696F10.1-RP11-119D18.1、RP11-78E6.1-RP11-71G7.1、RP11-79C6.1,IL7R-RP11-79C6.1、RTTN-SOCS6、SQSTM1P1-LINC00448、ZNF385B-SNORA43、ANKRD44、GPRIN3-RP11-115D19.1、TUSC3-PPM1AP1、RP11-644L4.1-FAM76B、及びBACE2からなる群から選ばれる少なくとも1の遺伝子の発現変化を決定する工程、又は遺伝子から翻訳された機能タンパク質の作用変化を評価する工程、及び
前記発現変化又は機能変化に基づき、候補薬剤のレチノイド感受性の制御を決定する工程
を含む、候補薬剤のスクリーニング方法にも関する。
からなる群から選ばれる、少なくとも一つの遺伝子多型が用いられる。
候補薬剤を含む溶液を適用する工程;
適用された細胞において遺伝子の発現変化を決定する工程;及び
前記発現変化に基づき、候補薬剤のレチノイド感受性に対する作用を決定する工程
を含む、候補薬剤のスクリーニング方法に関する。
候補薬剤を含む溶液を適用する工程;
適用された細胞において機能タンパクの作用への影響を評価する工程;及び
機能タンパク質の作用変化に基づき、候補薬剤のレチノイド感受性に対する作用を決定する工程
を含む、候補薬剤のスクリーニング方法に関する。
候補薬剤を含む溶液を適用する工程;
適用された細胞において遺伝子の発現を決定する工程;
適用された細胞において、機能タンパク質の作用への影響を評価する工程;及び
前記発現変化及び機能タンパク質の作用変化に基づき、候補薬剤のレチノイド感受性に対する作用を決定する工程
を含む、候補薬剤のスクリーニング方法に関する。
312名の被験者に対し、普段のスキンケアのお手入れに加えて、レチノール配合クリームを、4週間にわたって全顔に1日2回(朝夜)塗布した。4週間の連用塗布後、外観写真を撮影し、問診を行うとともに、皮膚所見を判定した。
252名の被験者に対し、普段のスキンケアのお手入れに加えて、レチノール配合美容液を、4週間にわたって、目及び口の周辺に1日2回(朝夜)塗布した。4週間の連用塗布後、外観写真を撮影し、問診を行うとともに、皮膚所見を判定した。
149名の被験者に対し、普段のスキンケアのお手入れに加えて、レチノール配合美容液を、2週間にわたって、目及び頬の周辺に1日2回(朝夜)塗布した。2週間の連用塗布後、外観写真を撮影し、問診を行うとともに、皮膚所見を判定した。
88名の被験者に対し、普段のスキンケアのお手入れに加えて、レチノール配合美容液を被験試料とし、被験試料からレチノールのみを抜去した製剤を対照試料として、それぞれ左顔面及び右顔面に分けて3カ月にわたり1日2回適用を行った後に、外観写真を撮影し、問診を行うとともに、皮膚所見を判定した。
79名の被験者に対し、普段のスキンケアのお手入れに加えて、レチノール配合美容液を被験試料とし、被験試料からレチノールのみを抜去した製剤を対照試料として、それぞれ左顔面及び右顔面に分けて9週間にわたり1日2回(朝夜)塗布した後に、外観写真を撮影し、問診を行うとともに、皮膚所見を判定した。
15名の被験者は、普段のスキンケアのお手入れに加えて、レチノール配合美容液をクリニックの医師の指導のもと使用した結果、皮膚トラブルが観察された方で、トラブル発生後に問診を行うとともに、皮膚所見を判定した。
試験1~6で得られた結果に基づき、被験者をレチノール感受性の反応群と健常群に分類した。具体的に、健常群は、レチノール試料の投与に対しトラブルが全く見られなかった被験者の群に関する。反応群は、副作用が明らかに認められ、レチノールに対する皮膚トラブルを経験した被験者の群に関する。反応群についてはさらに、強反応群、中反応群、弱反応群に分類した。弱反応群は、最大4日間にわたる弱い感覚刺激を呈する群として分類した。中反応群は、感覚刺激を呈しかつ皮膚所見を示す群、又は5日以上にわたり感覚刺激を呈する群として分類した。強反応群は、腫脹を伴う群、又は強い感覚刺激を呈しレチノールの使用を中止した群として分類した。
ロジスティック回帰分析の分析1でレチノイド感受性に影響が高い可能性のある遺伝子としてGPC5、WDR7、CAPSL、GPR1を選択し、分析2でレチノイド感受性に影響が高い可能性のある遺伝子としてGPC5、WDR7、SLC1A、CASP10を選択した。これらのうちGPR1はレチノイン酸レセプター結合性タンパク質に結合することが知られており、レチノイド感受性に影響があることが強く示唆された。さらにこれらの遺伝子がこれまでの知見と照らし合わせて、直接的あるいは間接的に皮膚感受性に影響があることが知られていることを調査することを目的に、QIAGEN社の提供するナレッジデータベースを用いて、遺伝子間の機能のパスウェイを文献レベルの知見から総合的に解析することを可能とするIngenuity Pathway Analysis (IPA)を用いて解析を行った。IPAによる解析により、CASP10、GPC5、WDR7、及びSLC1A6が間接的に複数の因子を介して皮膚感受性に影響を及ぼす可能性が示唆され、さらにその途中にNTRK1遺伝子が関与する可能性がわかった(図3)。NTRK1はNeurotrophic Receptor Tyrosine Kinase 1の遺伝子であり、同遺伝子産物は細胞分化に関与し、感覚神経のサブタイプの決定に関与することが知られ、その欠損は先天性無痛無汗症(Congenital insensitivity to pain with anhidrosis :CIPA)を引き起こすことが知られている。
Claims (7)
- 以下の:
rs66904991、rs192883707、rs75365663、rs3215895、rs12522083、rs151088833、rs117922874、rs62129325、rs7735423、rs180936202、rs12609658、rs5803510、rs35219727、rs76086616、rs74712856、rs10190756、rs182712478、rs583641、rs11264256、及びrs8112254からなる群から選ばれる、少なくとも1の遺伝子多型を検出する工程、
検出された遺伝子多型の種類又は数に応じて、レチノイドの皮膚外用における副作用に対する感受性を決定する工程
を含む、レチノイドの副作用に対する感受性の非診断的決定方法。 - 前記遺伝子多型が、rs66904991、rs192883707、rs75365663、rs3215895、rs12522083、rs117922874、rs12609658、及びrs10190756からなる群から選ばれる、少なくとも1の遺伝子多型である、請求項1に記載の決定方法。
- 前記遺伝子多型が、GPC5、RBMS3、WDR7、BACE2、CAPSL、GPR1、SLC1A6、及びCASP10からなる群から選択される少なくとも1の遺伝子に関与する遺伝子多型である、請求項1に記載の決定方法。
- 請求項1~3のいずれか一項に記載の方法により決定されたレチノイドの皮膚外用における副作用に対する感受性に基づく副作用に対する感受性に応じた化粧料の使用法の提供方法。
- 請求項1~3のいずれか一項に記載の方法により決定されたレチノイドの皮膚外用における副作用に対する感受性に基づいて化粧料を選択することを特徴とする、化粧料の提供方法。
- 候補薬剤を適用する工程、
適用された培養細胞において、下記の:GPC5、RBMS3、WDR7、BACE2、CAPSL、GPR1、SLC1A6、及びCASP10からなる群から選ばれる少なくとも1の遺伝子の発現変化を決定する工程、
前記発現変化に基づき、候補薬剤のレチノイド感受性についての作用を決定する工程
を含む、レチノイド感受性に対する作用について候補薬剤をスクリーニングする方法。 - 候補薬剤を適用する工程、
適用された培養細胞において、下記の:GPC5、RBMS3、WDR7、BACE2、CAPSL、GPR1、SLC1A6、及びCASP10からなる群から選ばれる少なくとも1の遺伝子から翻訳された機能タンパク質の作用変化を決定する工程、
前記機能タンパク質の作用変化に基づき、候補薬剤のレチノイド感受性についての作用を決定する工程
を含む、レチノイド感受性に対する作用について候補薬剤をスクリーニングする方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2019130064A JP7374634B2 (ja) | 2019-07-12 | 2019-07-12 | レチノイドの副作用に対する感受性の決定方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2019130064A JP7374634B2 (ja) | 2019-07-12 | 2019-07-12 | レチノイドの副作用に対する感受性の決定方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021013328A JP2021013328A (ja) | 2021-02-12 |
JP7374634B2 true JP7374634B2 (ja) | 2023-11-07 |
Family
ID=74530218
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019130064A Active JP7374634B2 (ja) | 2019-07-12 | 2019-07-12 | レチノイドの副作用に対する感受性の決定方法 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP7374634B2 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7046401B1 (ja) | 2021-04-26 | 2022-04-04 | 日本メナード化粧品株式会社 | 敏感肌の遺伝的素因の判定方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019044852A1 (ja) | 2017-08-31 | 2019-03-07 | 株式会社資生堂 | レチノイドの副作用に対する感受性の決定方法 |
-
2019
- 2019-07-12 JP JP2019130064A patent/JP7374634B2/ja active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019044852A1 (ja) | 2017-08-31 | 2019-03-07 | 株式会社資生堂 | レチノイドの副作用に対する感受性の決定方法 |
Non-Patent Citations (1)
Title |
---|
ALZOUBI, Karem H. et al.,The effect of genetic polymorphisms of RARA gene on the adverse effects profile of isotretinoin-trea,Int. J. Clin. Pharmacol. Ther.,2013年,Vol. 51,pp. 631-640 |
Also Published As
Publication number | Publication date |
---|---|
JP2021013328A (ja) | 2021-02-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Clausen et al. | Association of disease severity with skin microbiome and filaggrin gene mutations in adult atopic dermatitis | |
Betz et al. | Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci | |
Fryer et al. | Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans | |
Xu et al. | The emerging landscape of dynamic DNA methylation in early childhood | |
Shi et al. | Alterations in the intestinal microbiota of patients with severe and active Graves’ orbitopathy: a cross-sectional study | |
Wiśniowiecka-Kowalnik et al. | Application of custom-designed oligonucleotide array CGH in 145 patients with autistic spectrum disorders | |
Dolan et al. | A novel microdeletion/microduplication syndrome of 19p13. 13 | |
Levinsohn et al. | A somatic p. G45E GJB2 mutation causing porokeratotic eccrine ostial and dermal duct nevus | |
Mitsuhashi et al. | Exome sequencing identifies a novel SMCHD1 mutation in facioscapulohumeral muscular dystrophy 2 | |
Barber et al. | Duplications and copy number variants of 8p23. 1 are cytogenetically indistinguishable but distinct at the molecular level | |
Corso-Díaz et al. | Genome-wide profiling identifies DNA methylation signatures of aging in rod photoreceptors associated with alterations in energy metabolism | |
Yan et al. | Targeted next generation sequencing in 112 Chinese patients with intellectual disability/developmental delay: novel mutations and candidate gene | |
Huang et al. | DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence | |
Mehana et al. | LncRNA MEG3 regulates the interplay between Th17 and Treg cells in Behçet's disease and systemic lupus erythematosus | |
Melo et al. | Cutis Aplasia as a clinical hallmark for the syndrome associated with 19q13. 11 deletion: the possible role for UBA2 gene | |
JP7374634B2 (ja) | レチノイドの副作用に対する感受性の決定方法 | |
Tian et al. | The interactions of small proline-rich proteins with late cornified envelope proteins are involved in the pathogenesis of psoriasis | |
Steffensen et al. | High incidence of functional ion-channel abnormalities in a consecutive Long QT cohort with novel missense genetic variants of unknown significance | |
Castéra et al. | Fine mapping of whole RB1 gene deletions in retinoblastoma patients confirms PCDH8 as a candidate gene for psychomotor delay | |
Ozsoy et al. | Effect of AUTS2 gene rs6943555 variant in male patients with schizophrenia in a Turkish population | |
Kistol et al. | Leigh Syndrome: spectrum of molecular defects and clinical features in Russia | |
Kawamoto et al. | Further investigations of glucose-6-phosphate dehydrogenase variants in Flores Island, eastern Indonesia | |
JP7267198B2 (ja) | レチノイドの副作用に対する感受性の決定方法 | |
Banila et al. | A noninvasive method for whole-genome skin methylome profiling | |
Chow et al. | Effect of adalimumab on gene expression profiles of psoriatic skin and blood |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220603 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230530 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230728 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20231017 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20231025 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7374634 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |