WO2009053513A1 - Procédé et kit de détermination d'une prédisposition, d'un risque de développement ou du diagnostic du psoriasis - Google Patents

Procédé et kit de détermination d'une prédisposition, d'un risque de développement ou du diagnostic du psoriasis Download PDF

Info

Publication number
WO2009053513A1
WO2009053513A1 PCT/ES2008/070192 ES2008070192W WO2009053513A1 WO 2009053513 A1 WO2009053513 A1 WO 2009053513A1 ES 2008070192 W ES2008070192 W ES 2008070192W WO 2009053513 A1 WO2009053513 A1 WO 2009053513A1
Authority
WO
WIPO (PCT)
Prior art keywords
gene
psoriasis
lce3c
copies
risk
Prior art date
Application number
PCT/ES2008/070192
Other languages
English (en)
Spanish (es)
Inventor
Xavier ESTIVILL PALLEJÀ
Rafael Félix DE CID IBEAS
Lluís ARMENGOL DULCET
Original Assignee
Fundació Privada Centre De Regulació Genòmica (Crg)
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Fundació Privada Centre De Regulació Genòmica (Crg) filed Critical Fundació Privada Centre De Regulació Genòmica (Crg)
Publication of WO2009053513A1 publication Critical patent/WO2009053513A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • the present invention is related to molecular biology.
  • the present invention relates to a method and kit for determining a predisposition or a risk to develop a dermatological disease, in particular psoriasis.
  • Psoriasis is a chronic disease of the skin that occurs in different clinical forms: plaques, "guttata", erythrodermic and pustular. Although psoriasis affects all ethnic groups, its prevalence varies depending on the geographic location. The prevalence in northern Europe is close to 3%, in North America and in the United Kingdom it is 2%, while in Japan it is 0.2%, being rare in Native Americans. The concordance of psoriasis in monozygotic twins is 35-90%, compared to 12-30% in dizygotic twins, with an estimated heritability of 80-90%. Psoriasis affects both men and women and the first manifestation of the disease usually occurs in the third decade of life.
  • Psoriasis affects millions of people worldwide and does not have a curative treatment or there are no biological methods for its diagnosis, which is based on exclusively clinical criteria. On the other hand, there is no clear treatment modality for all individuals suffering from psoriasis.
  • psoriasis can lead to significant aesthetic disorders in the person, which may have psychological consequences for the individual suffering from the disease.
  • the location of genes possibly involved in dermatological pathologies such as psoriasis can be complex due to the imprecise definition of phenotypes, the heterogeneity and the uncertainty of the genetic transmission of the disease trait. It is considered that a diagnosis before the symptoms of the disease can emerge could prevent its occurrence or lessen its consequences.
  • HLA histocompatibility complex
  • HLA-Cw6 This region of the HLA corresponds to HLA-Cw6 and the locus in which it is found is known as PSOR1. Loci not linked to HLA have been detected on chromosomes 17q25 (PSORS2), 4q35 (PSORS3), 1q21 (PSORS4) and 3q21 (PSORS5). Despite these advances, none of the genes involved in this disease have yet been identified.
  • the present invention is based on the finding that a gene belonging to the cluster of late differentiation genes of the epidermal stratum corneum (in English “late cornified envelope”, abbreviated as "LCE”) is related to the predisposition or risk to which an individual develop psoriasis
  • LCE3C late differentiation gene of the epidermal stratum corneum 3C
  • the present invention refers to a procedure for the determination of a predisposition, a risk to be developed or the diagnosis of psoriasis, said procedure comprising: a) isolating a sample of nucleic acid from an individual; and b) analyze said sample, so that if the late differentiation gene of the epidermal stratum corneum 3C (LCE3C) is not detected or a decrease in the number of copies thereof is detected, it is indicative of a predisposition, risk to develop or Psoriasis diagnosis.
  • LCE3C epidermal stratum corneum 3C
  • LCE3C epidermal stratum corneum 3C
  • the late differentiation proteins of the epidermal stratum corneum are encoded by 13 genes located in the epidermal differentiation complex of chromosome 1 q21 (PSOR4) in a region of about two megabases.
  • group 3 contains five genes (LCE3A, LCE3B, LCE3AC, LCE3D and LCE3E) (see FIG. 1).
  • LCE3A, LCE3B, LCE3AC, LCE3D and LCE3E The expression of the LCE genes is induced by calcium and ultraviolet irradiation and the LCE proteins are part of the structural component of the corneal layer of the skin.
  • the cDNA sequences encoding these genes are available in public databases such as GenBank, where to access the cDNA sequence of LCE3A the accession number is NM_178431, of LCE3B is NM_178433, of LCE3C is NM_178434, of LCE3D is NM_032563 and of LCE3E is NM_178435).
  • GenBank GenBank
  • the genes that code for LCE are located on chromosome 1, specifically in region 1 q21.3.
  • kits for carrying out the step (b) of the process according to the first aspect of the invention are provided.
  • FIG. 1 represents the LEC gene cluster, according to the publication of Jackson et al.
  • the boxes show the intron-exon structures and the arrows indicate the direction of the transcription.
  • the exons of LCE3C are indicated separately (E1 -E3).
  • the numbers represent the distance between genes in kilobases.
  • the expression "at least one copy of the late differentiation gene of the epidermal stratum stratum 3C (LCE3C) is partially or completely deleted” means that when performing step (b) of the procedure or the LCE3C gene is not detected ( Which means that the only copy of said gene is deleted in the individual's sample) or a decrease in the number of copies of the gene is detected as a result of the total or partial deletion of one or more copies thereof with respect to controls well established (as illustrated below).
  • the late differentiation gene of the epidermal stratum corneum is not detected in the patient sample.
  • certain single nucleotide polymorphisms can be genotyped, which provide information on the total loss of LCE3C.
  • the genotype of certain single nucleotide polymorphisms is analyzed (as mentioned below) the genotype obtained will indicate whether or not there are copies of the gene.
  • the genotype is indicative that there is no copy of LCE3C
  • this will be indicative in turn that there has been complete deletion of the copy (s) of the LCE3C gene and consequently, that there is a predisposition or risk to develop psoriasis
  • the genotype obtained through the analysis of the polymorphisms is not conclusive (that is, it does not allow to determine that there is a complete absence of LCE3C)
  • the number of copies present in the patient sample is determined and compared with the number of copies of a specific control.
  • the term "totally or partially deleted” means that the entire gene is deleted or a fragment thereof (eg, an exon from LCE3C).
  • step (b) is carried out by analyzing at least one single nucleotide polymorphism in the cluster of late differentiation genes of the epidermal stratum corneum. These polymorphisms can be located in any of the genes that are part of said cluster as well as in the intergenic regions between these genes.
  • single nucleotide polymorphism or SNP means a region of a gene, or regulatory elements thereof, where the sequence of nucleotide bases can vary between individuals in a given nucleotide. There is often a predominant genotype that represents the usual form of a gene with subsets of a population that has a polymorphism that confers a different genotype. Certain polymorphisms may prevail in individuals of a particular ethnicity or specific geographic areas. A polymorphism may not affect the function of the gene, may lead to differences in the function of the gene, may produce an inactive product of the gene or may modulate the production of the product of the gene.
  • said polymorphism is selected from Table 1:
  • the polymorphisms that are part of the object of the invention are well known in the state of the art and additional information about them can be obtained in different public databases such as the NCBI (http: //www.ncbi.nlm.nih. gov) or Ia UCSC (http://www.genome.ucsc.edu).
  • the reference number (rs #) referred to in the present invention for each of the polymorphisms is that assigned by the NCBI and will be the form used hereafter to refer to them.
  • step (b) the polymorphism of a single nucleotide selected from the group consisting of: rs17659359, rs17659389, rs7516108, rs10888502, rs12046030, rs4112788 or combinations thereof are analyzed. More preferably single nucleotide polymorphisms are selected from rs4112788, rs17659359 and rs12046030.
  • step (b) is carried out by genotyping a single nucleotide polymorphism, so that if the genotype resulting from the analysis of the single nucleotide polymorphism rs4112788 or rs10888502, is homozygous CC, is indicative of the absence of the LCE3C gene (that is, none of said gene is detected in the individual's sample) and consequently, indicative that there is a predisposition for the individual to develop psoriasis.
  • the procedure object of the invention is carried out analyzing the polymorphisms located in the LCE3D and LCE3E genes, the CC genotype shows the highest degree of association with the absence of the LCE3C gene.
  • the association of the C allele of rs4112788 with the absence of LCE3C is such that 97.5% of the homozygous subjects for the C allele do not have the LCE3C gene.
  • This association has a statistical value of 3.14 E-85 (Table 3 below), which is indicative of the accuracy of the information that can be obtained when determining the predisposition or susceptibility to develop psoriasis.
  • none of the subjects homozygous for the T allele are homozygous for the absence of the LCE3C gene. This allows the use of SNP rs4112788 (and also others or their combinations) as a marker of the deletion of LCE3C, and consequently for the determination of a predisposition or risk to develop or diagnosis of psoriasis.
  • the alleles present in a sample are identified by determining the nucleotide present in one or more of the polymorphic points.
  • a series of methods for the identification of nucleotides present in polymorphic sites are known in the art.
  • genotype is not a critical aspect of the invention. Although for considerations of realization, cost and convenience some particular methods will be more desirable than others, it is clear that any method that can identify the present nucleotide will provide the necessary information to identify the genotype.
  • Preferred genotyping methods involve DNA sequencing, allele specific amplification or detection based on amplified nucleic acid probes.
  • the alleles of LCE3C and the cluster of LCE genes can be identified by DNA sequencing methods, such as the method of termination of the chain (Sanger et al., 1977, Proc. Nati. Acad Sci., 74: 5463-5467), which is well known in the field.
  • a sub sequence of the gene that includes the polymorphic site is amplified and cloned into a suitable plasmid and then sequenced, or sequenced directly. Based sequencing the PCR described in patent US 5,075,216 N 0. Normally, sequencing is performed using one of the Automatic DNA sequencers that are commercially available, including new generation based on DNA synthesis or DNA ligation.
  • the alleles of LCE3C and the other polymorphisms of the cluster of LCE genes can also be identified using genotyping methods based on amplification.
  • genotyping methods based on amplification.
  • Several methods of amplification of nucleic acids known in the art can be used to detect nucleotide changes in a target nucleic acid.
  • a preferred method is the reaction in polymerase chain (PCR), which is now well known in the art, and described in US Patents 4,683,195 0, 4,683,202 and 4,965,188.
  • PCR polymerase chain
  • the identification of the alleles only requires the detection of the presence or absence of the amplified target sequences.
  • the methods for the detection of the amplified target sequences are well known in the art.
  • Genotyping methods based on allele specific amplification can facilitate the identification of haplotypes, as described in the examples.
  • the allele specific amplification is used to amplify a region that includes multiple polymorphic sites of only one of the two alleles in a heterozygous sample.
  • variants of the SNP present in the amplified sequence are then identified, by means of the hybridization of probes or sequencing.
  • Probe - based genotyping can be performed using a test or "TaqMan""5'nuclease" as described in US Patent 5,210,015 N 0, 5,487,972 and 5,804,375.
  • TaqMan assay labeled detection probes are added that hybridize with the amplified region in the amplification reaction mixture. The probes are modified to prevent the probes from acting as primers for DNA synthesis. Amplification is performed using a DNA polymerase that has 5 'to 3' exonuclease activity.
  • any probe that hybridizes with the target nucleic acid following the primer to be extended is degraded by the 5 'to 3' exonuclease activity of the DNA polymerase. Therefore, the synthesis of a new target chain also results in the degradation of a probe, and the accumulation of the degradation product provides a measure of the synthesis of target sequences.
  • Any suitable method for the detection of the degradation product can be used in the TaqMan test.
  • the TaqMan assay can be used with allele-specific amplification primers so that the probe is used only to detect the presence of amplified product. Such an assay is performed as described for the kinetic PCR described above. Alternatively, the TaqMan assay can be used with a specific probe of the target.
  • the assay formats described above normally use labeled oligonucleotides to facilitate the detection of hybrid duplexes. The oligonucleotides can be labeled by the incorporation of a signal detectable by spectroscopic, photochemical, biochemical, immunochemical, radiological, radiochemical or chemical methods.
  • Useful tides include 32 P, fluorescent dyes, electrodensactive reagents, enzymes (as normally used in ELISAs), biotin or haptens and proteins for which antisera or monoclonal antibodies are available.
  • the labeled oligonucleotides of the invention can be synthesized and labeled using the techniques described above for oligonucleotide synthesis.
  • the probes that remain attached are detected by a first binding to the biotin of horseradish avidin-peroxidase (AHRP) or horseradish streptavidin-peroxidase (SA -HRP), which is then detected by carrying out a reaction in which the HRP catalyzes a color change of a chromogen.
  • AHRP horseradish avidin-peroxidase
  • SA -HRP horseradish streptavidin-peroxidase
  • the polymorphisms associated with psoriasis are analyzed. Using the information on the polymorphisms obtained can determine the risk of developing psoriasis with high precision. Therefore, the present invention is an effective means of knowing the risk of developing psoriasis before symptoms appear.
  • an auxiliary information useful for diagnosis is obtained, so that a suitable treatment can be designed and the prognosis can be improved.
  • Ia The present invention provides useful information in the clarification of the mechanism of development of psoriasis and is expected to contribute to the prevention and treatment of said disorders. In the same way, it is expected that the present invention can contribute to the development of new drugs that allow the treatment of psoriasis based on the presence of the polymorphisms indicated above.
  • step (b) is carried out by determining the number of copies of the LCE3C gene in the individual's sample, and comparing the resulting number of copies with the number of copies of the LCE3C gene identified. in a control sample.
  • control sample has been defined from the study of the number of copies of the LCE3C gene in samples belonging to the public HapMap project (http // www.hapmap.org).
  • the samples included in the study to determine the number of copies as controls have been; NA18515, NA18516, NA18517, NA19127, NA19128, NA19129.
  • All samples of the HapMap project have been studied by different methodologies regarding the presence of variations in the number of copies, and all the information is publicly accessible in the public database,
  • CNV complementation of copy number
  • LEC cluster and, in particular from the LCE3 sub-cluster, is known in the state of the art. It should also be noted that these CNV regions that include LCE3 sub-cluster genes have not been associated with any known pathology. There are public databases in which information is provided on the variations of copy number that include genes of the LCE3 sub-cluster.
  • CNV genotype with respect to the CNV in question that represents the usual genomic form with subsets of a population that has a CNV that has a different genotype
  • certain CNVs may prevail in individuals of a certain ethnicity or specific geographic areas.
  • a CNV can have consequences regarding the expression levels of a gene directly or indirectly, being able to affect the function of the gene, produce an inactive product thereof or modulate the production of the product of a gene that is found in the neighborhood.
  • the genotyping of CNVs is carried out in the alleles of the DNA sample, identifying the genomic region that defines the CNV of the LCE cluster (using in part the information available in the databases since this is still very inaccurate in terms of number of copies that the different subjects have).
  • Methods of identifying CNVs that include comparative genomic hybridization or molecular quantitative methods are well known in the state of the art.
  • Estivill and Armengol can be seen (cf. Estivill X., Armengol L. "Copy number variants and common disorders: Filling the gaps and exploring complexity in genome-wide association studies" PIoS Genetics, 2007 , in press) or Scherer et al. (cf. Scherer S. et al. "Challenges and standards in integrating surveys of structural variation” Nature Genetics, 2007, vol. 39, pS7-S15).
  • the procedure used to carry out the genotyping of CNVs is not a critical aspect of the invention.
  • SNPs that are part of the object of the invention allow the CNVs of the LCE region to be detected, being preferentially associated with the absence of the LCE3C gene or with a decrease in the number of copies of the gene.
  • Table 5a (below) describes these SNPs and their degree of association with the absence in homozygosis of the LCE3C gene.
  • the samples of the patients with the different clinical forms of psoriasis are selected to make the prediction or diagnosis based on the procedure according to the invention. This depends on the association between psoriasis and the specific SNP or CNV. These associations were established by the inventors by carrying out additional experiments and statistical analyzes, as explained below.
  • the proportion of data based on the association analysis allows the specialist to interpret the importance of the genotypes identified by sequencing the patient's DNA. In this way, the medical specialist can assess the probability that a patient has or develops psoriasis. It will be evident that the data relating the association of a particular genotype with a disorder can be provided to the user of the method according to the invention by incorporating an information sheet as part of a kit.
  • the present invention provides a kit comprising suitable means for carrying out the step (b) of the process according to the first aspect of the invention.
  • the kit may contain specific oligonucleotide probes for each of the polymorphisms, whether SNPs or CNVs, as well as instructions for their use. In some cases the detection probes may be fixed on a suitable support membrane.
  • the kit can also comprise amplification probes to amplify a region in which the polymorphism is found, such as primers. Alternatively, the kit may contain a set of primers comprising an allele-specific probe for the specific amplification of the alleles.
  • the kit may contain the reagents necessary to sequence the region containing the psoriasis-associated SNPs in the cluster of the LCE genes and the CNVs that contain them.
  • kits may include those necessary for Sanger type sequencing, synthesis or ligation.
  • Other optional components of the kit include additional reagents used in genotyping methods of SNPs or CNVs well known to those skilled in the art.
  • the kit can additionally comprise an agent that catalyzes the synthesis of primer extension products, reagents for the marking and / or detection of nucleic acid and buffers suitable for the amplification or hybridization reaction.
  • the kit comprises suitable means for carrying out the analysis of the single nucleotide polymorphisms of Table 1 or of the variation sequences of the copy number of Table 2. More preferably, suitable means comprise one or more oligonucleotides of specific sequence, each of the oligonucleotides comprising a sequence that hybridizes under strict conditions with at least one of the polymorphisms of Table 1 or with at least one of the variation sequences of the copy number of Table 2.
  • said suitable means comprise one or more oligonucleotides of specific sequence, each of the oligonucleotides comprising a sequence that hybridizes under strict conditions with the variable regions in copy number or CNVs or with nucleotide polymorphisms or SNPs.
  • SNPs were selected from the public database dbSNP version db124 (http://www.ncbi.nlm.nih.gov/) by placing LCE the search engine and selecting SNPs in humans.
  • the SNPs from the HapMap public database http://www.hapmap.org
  • assembly B34 of NCBI and dbSNP124 were selected.
  • those SNPs with a frequency greater than 10% were selected in the European sample (CEU) and located in an LCE region.
  • SNPs All SNPs were genotyped using the SNPlex system (Applied Biosystems). The SNPs were launched to design using the tool provided by Applied Biosystems on their website
  • the oligonucleotides for genotyping were designed and manufactured by Applied Biosystems (Applied Biosystems, Foster City, CA). For genotyping, a slightly modified protocol was originally followed by the one originally indicated by the manufacturer (Tobler AR, et al., "The SNPlex genotyping system: a flexible and scalable platform for SNP genotyping", J Biomol Tech, 2005, vol. 16 (4 ), p. 398-406). All reactions were done in 384-well plates using several liquid handling robots. Specifically, 12 ul of each DNA sample to 75 ng / .mu.l boiling fragmented to 99 0 C for 10 minutes.
  • Two microliths (150 ng) were dehydrated in a 384 well plate.
  • the ligation reaction was carried out, for each well, in a total volume of 5 ⁇ l containing 2.3 ⁇ l of water without nucleases, 2.5 ⁇ l of oligonucleotide mixture, 0.05 ⁇ l of universal linkers, 0.1 ⁇ l of probes and 0.05 ⁇ l of dATP (100x).
  • the PCR reaction consisted of an initial heating at 48 0 C of 30 minutes, initial denaturation at 9O 0 C for 20 minutes, 25 cycles of denaturation at 94 0 C for 15 seconds, hybridization at 6O 0 C for 30 seconds and extension to 51 0 C for 30 seconds (with 3% increase), final extension at 99 0 C for 10 minutes and maintenance at 4 0 C until the next step.
  • washing of the PCR with exonuclease was carried out, for each well, in a final volume of 5 ⁇ l containing 4.2 ⁇ l of water without nucleases, 0.5 ⁇ l of buffer of the exonuclease, 0.2 ⁇ l of lambda exonuclease and 0.1 .mu.l of exonuclease I. the plates were kept in a thermocycler for 90 minutes at 37 0 C, followed by 10 minutes at 8O 0 C and holding at 4 0 C until the next step.
  • the final amplification reaction was carried out, for each well, in a final volume of 7.92 ⁇ l containing 2.42 ⁇ l of water without nucleases, 5 ⁇ l of SNPLexAMp Mastermix and 0.5 ⁇ l of oligonucleotides (2Ox).
  • the PCR reaction consisted of an initial denaturation at 95 0 C for 10 minutes, 30 cycles of denaturation at 95 0 C for 15 seconds, hybridization at 63 0 C for 1 minute and maintenance at 4 0 C until the next step.
  • the CC genotype can be used as an indirect marker of the presence of the deletion in homozigosis of the LCE3C gene, and that on the other hand individuals carrying the CC genotype have an increased risk of suffer from psoriasis, and can be used as a risk marker for the disease.
  • the identification of the region of the LCE3C gene involved in psoriasis was identified based on comparative genomic hybridization (CGH) experiments using the Agilent 244K array (following the manufacturer's instructions). The analysis identified a region of 4 contiguous probes that showed a decrease in the intensity of the hybridization (Odds Ratio> 0.3) in the psoriasis samples with respect to the control samples.
  • the region involves Agilent probes A_16_P15296679, A_14_P100633,
  • a probe for LCE2C and another for LCE3E in Table 5 were selected in order to confirm that said genes were not affected (control) and, consequently, to rule out their possible involvement in the disease.
  • the frequency of completely or partially deleted samples was compared with respect to those with one or more copies of the LCE3C gene.
  • Table 6 shows the results of the study with the TaqMan probe of LCE3C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne une méthode consistant a) à isoler un échantillon d'acide nucléique d'un individu; et b) à analyser ledit échantillon de manière que, si le gène de différenciation tardive de la couche cornée épidermique 3C (LCE3C) n'est pas détecté, ou bien si une diminution du nombre de copies de celui-ci est détectée, cela indique une prédisposition, un risque de développement ou un diagnostic du psoriasis. L'invention concerne également des kits permettant de mettre en oeuvre ladite méthode. La méthode et le kit de l'invention permettent d'obtenir des informations auxiliaires utiles pour le diagnostic, afin de mettre au point un traitement adapté et d'améliorer le pronostic de ce type de pathologies.
PCT/ES2008/070192 2007-10-24 2008-10-21 Procédé et kit de détermination d'une prédisposition, d'un risque de développement ou du diagnostic du psoriasis WO2009053513A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES200702856 2007-10-24
ESP200702856 2007-10-24

Publications (1)

Publication Number Publication Date
WO2009053513A1 true WO2009053513A1 (fr) 2009-04-30

Family

ID=40579117

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES2008/070192 WO2009053513A1 (fr) 2007-10-24 2008-10-21 Procédé et kit de détermination d'une prédisposition, d'un risque de développement ou du diagnostic du psoriasis

Country Status (1)

Country Link
WO (1) WO2009053513A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109207575A (zh) * 2017-07-02 2019-01-15 复旦大学附属华山医院 一种用于预测甲氨蝶呤治疗银屑病临床疗效的基因标志物及检测试剂盒
CN109295194A (zh) * 2017-07-25 2019-02-01 复旦大学附属华山医院 银屑病易感基因lce3d和tnip1及其用途

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BOWCOCK A. M. ET AL.: "Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies", HUMAN MOLECULAR GENETICS., vol. 10, no. 17, 15 August 2001 (2001-08-15), pages 1793 - 1805 *
CAPON F. ET AL.: "Fine mapping of the PSORS4 psoriasis susceptibility region on chromosome 1q21", THE JOURNAL OF INVESTIGATIVE DERMATOLOGY., vol. 116, no. 5, May 2001 (2001-05-01), pages 728 - 730 *
GIARDINA E. ET AL.: "Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus", ANNALS OF HUMAN GENETICS., vol. 68, no. 6, November 2004 (2004-11-01), pages 639 - 645 *
GIARDINA E. ET AL.: "Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic dermatitis (ATOD2) on human chromosome 1q21", HUMAN HEREDITY., vol. 61, no. 4, September 2006 (2006-09-01), pages 229 - 236 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109207575A (zh) * 2017-07-02 2019-01-15 复旦大学附属华山医院 一种用于预测甲氨蝶呤治疗银屑病临床疗效的基因标志物及检测试剂盒
CN109207575B (zh) * 2017-07-02 2022-02-11 复旦大学附属华山医院 一种用于预测甲氨蝶呤治疗银屑病临床疗效的基因标志物及检测试剂盒
CN109295194A (zh) * 2017-07-25 2019-02-01 复旦大学附属华山医院 银屑病易感基因lce3d和tnip1及其用途
CN109295194B (zh) * 2017-07-25 2022-02-11 复旦大学附属华山医院 银屑病易感基因lce3d和tnip1及其用途

Similar Documents

Publication Publication Date Title
Korostishevsky et al. Is the G72/G30 locus associated with schizophrenia? Single nucleotide polymorphisms, haplotypes, and gene expression analysis
US20080305967A1 (en) Genetic Markers Associated with Endometriosis and Use Thereof
US20220002810A1 (en) Methods and compositions for correlating genetic markers with prostate cancer risk
US8712696B2 (en) Methods of prognosing a rheumatoid arthritis remission phenotype
MXPA06003828A (es) Uso de polimorfismos geneticos que se asocian con la eficacia del tratamiento de enfermedad inflamatoria.
US20100092959A1 (en) Single nucleotide polymorphisms as genetic markers for childhood leukemia
WO2010124101A2 (fr) Marqueurs génétiques associés à l'endométriose et utilisation de ceux-ci
AU2013301606A1 (en) Genetic markers for predicting responsiveness to FGF-18 compound
US20200087728A1 (en) Genetic markers associated with endometriosis and use thereof
US20050255498A1 (en) APOC1 genetic markers associated with age of onset of Alzheimer's Disease
EP2393939B1 (fr) Marqueur snp de risque du cancer du sein et des ovaires
WO2009053513A1 (fr) Procédé et kit de détermination d'une prédisposition, d'un risque de développement ou du diagnostic du psoriasis
US20140255930A1 (en) Materials and Methods Related to Dopamine Dysregulation Disorders
KR20230005816A (ko) 신경전달물질 수송체 억제제의 효능을 평가하기 위한 조성물 및 방법
CN113166810A (zh) 包括gba基因单碱基多态性的脑动脉瘤诊断用snp标志物
JP2007517511A (ja) ヒトチオプリンｓ−メチルトランスフェラーゼ欠損に関連するハプロタイプおよび多型
KR20170049768A (ko) 피부 색상 및 흑화 민감도 진단용 단일염기다형성 마커 및 이의 용도
KR101546069B1 (ko) 대사증후군 예측용 ｓｎｐ 마커 및 이의 용도
JP6516128B2 (ja) 抗甲状腺薬誘発性無顆粒球症リスクを判定するための検査方法及び判定用キット
KR102158716B1 (ko) Arhgap32 유전자의 단일염기다형성을 포함하는 뇌동맥류 진단용 snp 마커
WO2009101619A2 (fr) Procédés pour prédire la réponse d'un patient à un traitement au lithium
US20200095638A1 (en) Methods for identifying and treating kawasaki disease patients with intravenous immunoglobulin resistance
EP3922733A1 (fr) Marqueur de polymorphisme mononucléotidique pour le diagnostique de la puberté précoce ou son pronostic thérapeutique, et utilisation correspondante
KR20240057772A (ko) 우울증 진단용 단일염기다형성 및 이의 용도
US20130078637A1 (en) Antipsychotic-induced parkinsonism genotypes and methods of using same

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08842372

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08842372

Country of ref document: EP

Kind code of ref document: A1