KR100726800B1 - Polymorphism in phosphoenolpyruvate carboxykinase 1 - Google Patents

Abstract

The present invention relates to the association of polymorphism in high concentration lipoprotein and triglyceride levels in Phosphoenolpyruvate Carboxykinase 1 (PCK1). In the present invention, one of the haplotype PCK1-ht3 was confirmed to have a sensitive effect on the risk of T2DM (type 2 diabetes mellitus). The genetic association between the mutation / haplotype information and HDL (high density lipoprotein) and TG (triglyceride) identified in the present invention can be usefully used for the study of genetic epidemiology of important genes.

HDL, Type 2 Diabetes Mellitus, PCK, Polymorphism, TG

Description

Phosphoenolpyruvate carboxykinase 1 gene polymorphism {Polymorphism in phosphoenolpyruvate carboxykinase 1}

1A shows the polymorphisms identified in PCK1 on chromosome 20q13.31 (reference genomic sequence NT_011362.9).

1B shows the haplotype of PCK1.

1C shows the polymorphisms identified in PCK2 on chromosome 14q11.2 (reference genomic sequence NT_026437.11).

1D shows the haplotype of PCK2.

2A-2N show sequence chromatograms of 14 polymorphisms in PCK1. Arrows indicate polymorphic sites.

1.Beale EG, Hammer RE, Antoine B, Forest C (2004) Disregulated glyceroneogenesis: PCK1 as a candidate diabetes and obesity gene. Trends Endocrinol Metab 15: 129-135

Nordlie RC, Lardy HA (1963) Mammalian liver phosphoneolpyruvate carboxykinase activities. J Biol Chem 238: 2259-2263

Modaressi S, Christ B, Bratke J, Zahn S, Heise T, Jungermann K (1996) Molecular cloning, sequencing and expression of the cDNA of the mitochondrial form of phosphoenolpyruvate carboxykinase from human liver. Biochem J 315 (Pt 3): 807-814

Watford M, Hod Y, Chiao YB, Utter MF, Hanson RW (1981) The unique role of the kidney in gluconeogenesis in the chicken. The significance of a cytosolic form of phosphoenolpyruvate carboxykinase. J Biol Chem 256: 10023-10027

5.Beale EG, Forest C, Hammer RE (2003) Regulation of cytosolic phosphoenolpyruvate carboxykinase gene expression in adipocytes. Biochimie 85: 1207-1211

She P, Shiota M, Shelton KD, Chalkley R, Postic C, Magnuson MA (2000) Phosphoenolpyruvate carboxykinase is necessary for the integration of hepatic energy metabolism. Mol Cell Biol 20: 6508-6517

7. Zouali H, Hani EH, Philippi A, Vionnet N, Beckmann JS, Demenais F, et al. (1997) A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene. Hum Mol Genet 6: 1401-1408

8. Hani el H, Zouali H, Philippi A, Beaudoin JC, Vionnet N, Passa P, et al. (1996) Indication for genetic linkage of the phosphoenolpyruvate carboxykinase (PCK1) gene region on chromosome 20q to non-insulin-dependent diabetes mellitus. Diabetes Metab 22: 451-454

9. Bell GI, Xiang KS, Newman MV, Wu SH, Wright LG, Fajans SS, et al. (1991) Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. Proc Natl Acad Sci U S A 88: 1484-1488

10. Wilson BD, Ollmann MM, Kang L, Stoffel M, Bell GI, Barsh GS (1995) Structure and function of ASP, the human homolog of the mouse agouti gene. Hum Mol Genet 4: 223-230

11.Committee E (1997) Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20: 1183-1197

12. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419

13.Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5 'nuclease assay. Genet Anal 14: 143-149

14. Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68: 978-989

15.Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA (2002) Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 70: 425-434

16. Cao H, van der Veer E, Ban MR, Hanley AJ, Zinman B, Harris SB, et al. (2004) Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus. J Clin Endocrinol Metab 89: 898-903

Field of technology

The present invention relates to polymorphism of genes associated with disease. More specifically, the present invention relates to phosphoenolpyruvate carboxykinase 1 (PCK1) polymorphisms associated with high density lipoprotein (HDL) and triglyceride (TG) levels.

Prior art

Phosphoenolpyruvate carboxykinase (PCK) functions primarily as an enzyme to help regulate gluconeogenesis and is involved as a candidate gene for type 2 diabetes mellitus (T2DM). The PCK gene is located in both cytosol (PCK1; MIM 261680) and mitochondria (PCK2; MIM 261650) [supra, 1, 2]. Similar gene structures and 68-70% high nucleotide / amino acid sequence homology between the cell substrate PCK1 and mitochondrial PCK2 genes suggest that they are from a common ancestor gene. The activity of PCK1 (on chromosome 20q13.31) is controlled by the transcription rate of its gene, which regulates physiologically necessary glucose production by being regulated by insulin, glucocorticoids, cAMP and food. 4] On the other hand, mitochondrial PCK2 (on chromosome 14q11.2) is believed to be constitutive [supra: 4]. PCK1 has been suggested to be optimal for glucose neosynthesis from amino acids and mtPCK2 is optimal for glucose neosynthesis from lactates [4]. Recent evidence suggests that PCK may function more as an integrator of hepatic energy metabolism than as a determinant of glycosynthesis [1, 5, 6].

Previous studies have suggested that the PCK1 gene region on chromosome 20q has a genetic association with T2DM. Using the affected sib pair method, significant results were obtained in the 20q13 region, that is, near the PCK1 locus [7]. It has also been reported as a candidate region for insulin resistance [8]. In addition, two other diabetic genes are mapped to chromosome 20q, both of which are located in the centromere for the PCK1 locus, which genes are present in adolescent onset diabetes of the young (MODY) MODY1 gene which causes a subtype of and a human homologue of the murine gene responsible for obesity-diabetes syndrome in mice (Agouti signaling protein) ASP gene (see above, 9, 10).

In an effort to identify (identify) genetic polymorphisms in potential candidate genes for T2DM, we included a PCK gene, including a 1.5 kb 5 'flanking region and +/- 50 bp exon-intron boundaries. The present invention was completed by analyzing the sequence of all exons in ( PCK1 and PCK2 ) and investigating the association between the risk of T2DM and the diabetic phenotype in diabetic studies of Korean population.

It is an object of the present invention to provide a study of genetic polymorphisms in potential candidate genes for type 2 diabetes mellitus (T2DM).

Specifically, an object of the present invention is to provide a phosphoenolpyruvate carboxykinase 1 (PCK1) polymorphism associated with high density lipoprotein (HDL) and triglyceride (TG) levels.

To this end, we analyzed the sequence of all exons in the PCK ( PCK1 and PCK2 ) genes and examined the association of diabetes phenotype with T2DM in the Korean population (775 patients with T2DM and 316 normal controls). Twenty-two polymorphisms in PCK1 and PCK2 in the Korean population (n = 24) were confirmed by direct DNA sequencing. TaqMan genotyping was used for large scale genotyping. The risk of T2DM and its association with diabetes phenotype and PCK polymorphisms were analyzed using logistic and multiple regression, adjusting age, gender and BMI (body mass index). No significant association was detected between the risk of T2DM and genetic polymorphisms in the PCK gene, but further haplotype analysis revealed that PCK1-ht3 , one of the common haplotypes, has a sensitive effect on the risk of T2DM ( P = 0.006). In addition, one 3 'UTR SNP showed a dramatic association with HDL (high density lipoprotein) levels among non-diabetic controls: the lowest HDL level among individuals with homozygotes (T / T) for major alleles. (42.73 ± 12.37 mg / dl), medium level among subjects with heterozygotes (T / C) (48.96 ± 14.45 mg / dl), and subjects with homozygotes (C / C) for minor alleles Among the highest levels (53.53 ± 10.82 mg / dl) (P = 0.000003). In addition, the 3 ′ UTR SNP was associated with triglyceride (TG) levels: individuals with homozygotes (C / C) for minor alleles showed lower TG levels than those without.

In the preceding report [16] supra, absolute LD (| D '| = 1 with 3 adjacent SNPs ( -1399C> T: -1269C> T: -534C> G: + 69A> G , see FIG. 1A). And r ² One promoter SNP in = 1) (-232C>G;534C> G in the present invention) has been reported to be associated with the risk of T2DM in both Oji-Cree and Caucasian communities. However, no significant association was found in the Korean population. Only PCK1-ht3 showed significant association with the risk of T2DM. Although it is difficult to resolve the contradiction between previous studies and the present invention, their interactions between different genetic backgrounds and environmental factors or different ethnic groups may be plausible explanations. In the present invention, the significance for association with HDL in 3 'UTR SNPs (P = 0.000003 in co-dominant model) was maintained even after the most stringent correction for multiple experiments (170 trials: 17 comparisons in patient / control) , 17 comparisons in five different diabetic phenotypes [CHOL, TG, HDL, insulin and BMI] using three alternative analytical models (co-dominant, dominant and recessive models).

Although functional evidence (s) associated with different HDL and TG levels mediated by alternative genotypes in the 3 'UTR are not currently understood (lightened), polymorphisms in the 3' UTR alter the secondary structure and translational efficacy of RNA. Gene function by affecting motifs in RNA that bind to proteins that regulate RNA degradation. Recent data suggest that PCK1 is associated with glyceroneogenesis as well as glucose neosynthesis [1]. Glycerone genesis in both liver and adipose tissue is the de novo synthesis of glycerol 3 phosphate from precursors of glucose synthesis. Each glycerol 3 phosphate is used to esterify fatty acyl CoA to form TG. Mice lacking liver PCK1 have been found to develop fatty liver and have elevated plasma fatty acid and TG levels after fasting [6]. These results indicate that mutations in the PCK1 gene may affect glyceronene genesis, which will affect the storage and release of fatty acids. Additional biological and / or functional evidence will be needed to clarify the mechanism (s) associated with different blood HDL- and TG-concentrations mediated by alternative PCK1 polymorphisms. In summary, 22 polymorphisms in PCK1 and PCK2 were identified in the Korean population (n = 24) by direct DNA sequencing. The association between PCK polymorphisms and the risk of T2DM and the diabetic phenotype was analyzed using logistic and multiple regression methods, adjusting for age, gender and BMI. Although no significant association was detected between genetic polymorphism in the PCK gene and the risk of T2DM, PCK1-ht3 was found to have a significant association with the risk of T2DM. One 3 'UTR SNP also showed a dramatic association with HDL and TG levels in non-diabetic controls. The strong association of HDL and TG levels with PCK1 polymorphism and the variant / haplotype information identified in the present invention will be useful for genetic epidemiological studies of other metabolic diseases.

The present invention is described based on the following examples. The following examples are intended to illustrate the invention, not to limit the invention. All documents disclosed in the present invention are incorporated by reference.

Example

Example 1 Selection of Subjects

All 775 non-related patients with T2DM and 316 non-related non-diabetic control subjects were recruited. Non-diabetic control subjects were recruited from non-selective populations who had routine health check-ups at Seoul National University Hospital (Seoul, Korea). Inclusion criteria were as follows: age 60 years or older, lack of previous diabetes diagnosis, absence of diabetic patients in the family within 1 village, fasting plasma glucose concentration of less than 6.1 mmol / l and HbA1c of less than 5.8%. Diabetic subjects were randomly recruited from patients who visited outpatient clinics at Seoul National University Hospital (Seoul, Korea). Diabetes was diagnosed based on the ADA criteria [11]. Subjects with positive GAD antibodies were excluded. All patients enrolled in the present invention were Korean ethnicity. This study protocol was approved by the Institutional Review Board of the Seoul National University Hospital. Informed consent was obtained from all subjects prior to blood collection. All subjects were examined in the morning after overnight fast. Height, weight, waist and hip circumference and blood pressure were measured. Biochemical measurements of blood samples (fasting plasma glucose, glucose after 2 hours postprandial, fasting plasma insulin, HbA1c, total cholesterol, triglycerides and high-density lipoprotein (HDL)) and DNA extraction were performed. Insulin Tolerance Index HOMAIR (homeostasis model assessment) was calculated as fasting serum insulin (pmol / l) x fasting plasma glucose (mmol / l) / 135 [supra: 12]. The clinical characteristics of the subjects are shown in Table 1.

Table 1. Clinical Features of Type 2 Diabetics and Normal Controls

Data is mean ± SD. HOMA-IR refers to homeostasis model evaluation of insulin resistance

^A P -value <0.001, ^b P -value <0.01 for the difference between T2DM and normal control

Example 2: Human PCK  Gene Sequence Analysis

We used an ABI PRISM 3700 DNA analyzer (Applied Biosystems, Foster City, Calif.) To detect all exons, including exon-intron boundaries and promoter regions (approximately 1.5 kb), to detect SNPs in 24 Korean DNA samples. Sequencing was performed. 24 primer sets for amplification and sequencing were designed based on GenBank sequences (reference sequences of PCK1 mRNA: NM_133262 and mRNA: NT_026437.11). Table 2 shows the primers for PCK1 sequence analysis. Information on primers is available at http://www.snp-genetics.com/user/additional_list.asp. Sequence variation was confirmed by chromatogram (see FIGS. 2A-2N).

Table 2. Primer Sequences for PCK1 and PCK2 Sequence Variation Screening

Example 3: Genotyping Using Polarization Detection

For genotyping of polymorphic sites, amplification primers and probes were designed for TaqMan (see above). Primer Express (Applied Biosystems) was used to design both PCR primers and MGB TaqMan probes. One allele probe was labeled with FAM dye (6-carboxyfluorescein, blue) and the other was labeled with fluorescent VIC dye (6-carboxyfluorescein, green). PCR was performed on a TaqMan Universal Master Mix without UNG (Uracil-N-Glycosylase) at a PCR primer concentration of 900 nM and TaqMan MGB-probe concentration of 200 nM. The reaction was performed in 384-well format using 20 ng genomic DNA with a total reaction volume of 5 ul. The plate was then placed in a thermal cycler (PE 9700, Applied Biosystems) and heated at 50 ° C. for 2 minutes and at 95 ° C. for 10 minutes followed by 40 cycles of 15 seconds at 95 ° C. and 1 minute at 60 ° C. TaqMan assay plates were transferred to Prism 7900HT instrument (Applied Biosystems) to read the fluorescence intensity in each well of the plate. Fluorescence data obtained from each plate was analyzed using automated software (SDS 2.1). Table 3 shows the primers used in this experiment. Information on primers is available on the Applicant's website (http://www.snp-genetics.com/user/additional_list.asp).

Table 3. Amplification Sequences and TaqMan Probes for PCK SNP Genotyping

Example 4: Statistical Analysis

The χ ² test was used to determine whether individual variations in the cluster were in equilibrium (Hardy-Weinberg equilibrium) at each locus. Haplotypes and their frequencies were inferred using the algorithm developed by Stephens et al. [14]. P values were calculated using logistic regression analysis, which controls age, gender and BMI as covariates. Multiple regression methods were used to analyze the association of metabolic phenotypes with adjusting age, sex and BMI. While controlling age, gender and BMI as covariates, the haplotype associations were analyzed using the algorithms developed by Schaid et al. [15] above (Haplo.Score and Haplo.GLM). Insulin and TG levels were log-transformed to normalize the aura distribution. Since treatment of T2DM could affect phenotypic values in diabetic patients, only non-diabetic subjects were used for association analysis of metabolic phenotypes.

result

14 polymorphisms were identified (identified) in PCK1 : 5 in the 5 'flanking region, 2 in the introns, 5 in exons and 2 in 3' UTRs. Eight polymorphisms were identified in PCK2 : two in the 5 'flanking region, one in intron and four in exon (website (http://www.snp-genetics.com/user/additional_list.asp) See Table 4 and Table 5). The locations and allele frequencies of the identified polymorphic sites are shown in FIGS. 1A and 1B. FIG. 1 b shows haplotypes with a frequency greater than 0.05, with the rest ^* including rare haplotypes: GCGTTC, ACGCTT, AGCTTT, ACGCTC, GGGTGT, GCCTTT, AGGTTT, AGGCGT, GGGTTT, GCGTGC, ACGCGC, GCGCGT , GCGCTT, ACCTGT, GCCTTC, ACGTTT, GCGCGC, GGGCTT, ACCTGC, GGGCGT, GCCTGT, AGCCTT, ACCCTC, ACCCTT, GCGCTC, AGGCGC, and ACGTTC. By pair-wise association analysis using 24 Korean DNA samples used for direct sequencing, we found that two sets of SNPs in PCK1 are in absolute LD (D ′ = 1 and r ² = 1). Found (see FIG. 1A). Among the polymorphisms identified, six SNPs in PCK1 ( + 69A> G, + 1428C> G, + 1573G> C, + 3404T> C, + 4513T> G and + 4824T> C ) and four SNPs in PCK2 ( − 403C> T, + 3894T> C, + 5804A> G and + 8881C> G ) were selected for large scale genotyping based on location, LDs, frequency and haplotype tagging status. The sequence position in the SNPs is based on the translation start site of the gene. Six universal haplotypes in PCK1 and four universal haplotypes in PCK2 were constructed in the Korean population (see FIGS. 1B and 1D). 1D shows the haplotype with a frequency of greater than 0.02. The remaining ^** include rare haplotypes: TTGG, TCGG, CCGC, CCAG, and CTGC. The minor allele frequencies of genotyped polymorphisms were 0.391 ( PCK1 + 69A> G (Leu23Leu) ), 0.27 ( PCK1 + 1428C> G (Leu184Val) ), 0.281 ( PCK1 + 1573G> C ), and 0.356 ( PCK1 ) in the Korean population. + 340C> T ), 0.216 ( PCK1 + 4513T> G ), 0.222 ( PCK1 + 4824T> C ), 0.487 ( PCK2-403C> T ), 0.202 ( PCK2 + 3894T> C (Pro124Pro) ), 0.212 ( PCK2 + 5804A > G (Lys410Lys) ) and 0.364 ( PCK2 + 8881C> G ) (n = 1,091, see FIG. 2). All locus genotype distributions were at Hardy-Weinberg equilibrium (P> 0.05, see Table 5).

Table 4. Frequency of PCK1 Gene Polymorphisms in Korean Subjects

Table 5]. Frequency of PCK1 and PCK2 Gene Polymorphisms in Korean Subjects

^a Naming from ^a prior study [16]

^b P value for deviation from HWE or normal control (n = 316, bold typeface) among 24 samples used for sequencing

Of the common haplotypes identified in the Korean population, only haplotypes with a frequency greater than 0.05 were used for further analysis (see FIGS. 1B and 1D). Haplotype tagged almost (> 90%) by a single SNP was not used for further studies (ht2 in PCK1; ht3 in PCK2). The association of PCK polymorphisms with the risk of T2DM and the diabetic phenotype was analyzed using logistic and multiple regression methods adjusting age, sex and BMI (775 T2DM patients and 316 normal controls). The clinical characteristics of the subjects are listed in Table 1. Only non-diabetic subjects were used for the association analysis of metabolic phenotypes including cholesterol (CHOL), log-converted triglycerides (TG), high-density lipoproteins (HDL), log-converted insulin, and BMI. This is because treatment for T2DM can affect these values. No significant association was detected between genetic polymorphism in the PCK gene and the risk of T2DM, but further haplotype analysis revealed that PCK1-ht3 , one of the common haplotypes, has a sensitive effect on the risk of T2DM. (P = 0.006, see Table 6).

Table 6. Logistic Analysis of PCK Polymorphism and Type 2 Diabetes Among Patients and Normal Subjects

P-values for logistic analysis for co-dominant models controlling age, gender and BMI as minor allele frequencies and covariates of each site were presented. The ^a P-value for Haplotype association was calculated by an algorithm developed by Schaid et al. (Haplo.Score, supra), which controls age, sex and BMI as covariates.

Some SNPs and haplotypes have significant correlations with several metabolic traits (cholesterol: PCK1 + 3404T> C and PCK1-ht1 log converted triglycerides: PCK1 + 4824T> C and PCK1-ht1 high density lipids: + 1428C> G, + 4824T> C and PCK1-ht3 ) (see Table 7).

Table 7. PCK polymorphism and cholesterol (CHOL), log-converted triglycerides (log [TG]), and high-density lipoproteins (HDL), which control age, sex, and BMI as covariates among non-diabetic subjects. Regression analysis

^a C / C, C / R and R / R denote homozygotes for universal alleles and heterozygotes and homozygotes for rare alleles, respectively. Haplotypes and their frequencies were inferred using the algorithm developed by Stephens et al. [14]. Genotype and haplotype distribution (mean ± SD of cholesterol (mg / dl), Log [TG (mg / dl)] and HDL (mg / dl), and P-values (co-dominant, dominant for regression analysis) And recessive model). The bP values for the haplotype associations were calculated using an algorithm (Haplo. GLM) developed by Schaid et al. [15], which controls age, gender and BMI as covariates.

One of these 3 'UTR SNPs, + 4824T> C, showed a dramatic and gene-dependent association with HDL levels in non-diabetic controls: with homozygotes (T / T) for major alleles Homozygous (C /) for the median level (48.96 ± 14.45 mg / dl) and minor alleles in subjects with the lowest HDL level (42.73 ± 12.37 mg / dl), heterozygotes (T / C) in the subject Highest level in subjects with C) (53.53 ± 10.82 mg / dl) (P = 0.000003, see Table 6). In addition, the 3 'UTR SNP was associated with TG levels: lower TG levels were found in individuals with homozygotes (C / C) for minor alleles than in those not. In a further analysis, 3 'UTR SNP and PCK1-ht3 showed significant association with BMI in diabetic subjects (P = 0.002 and P = 0.0002, respectively), but this significant association was associated with phenotypic values in patients treated with T2DM. It was unreliable because it could affect it (see Table 8).

Table 8. PCK Polymorphism and Body Obesity Index (BMI), Waist / Hip Ratio (WHR), Total Cholesterol (CHOL), Log-Converted Triglycerides (Log) Controlling Age, Gender, and BMI as Covariates in Diabetic Subjects [TG]) and regression analysis with high-density lipoprotein (HDL)

(Continued Table 8)

^a C / C, C / R and R / R denote homozygotes for universal alleles and heterozygotes and homozygotes for minor alleles, respectively.

Genotype and haplotype distribution (BMI (Kg / m ² ), waist / hip ratio, total cholesterol (mg / dl), log-converted triglycerides (Log [TG (mg / dl)]) and HDL (mg / dl) mean ± SD), and P-values (co-dominant, dominant and recessive models for regression analysis).

In addition, PCK polymorphism and log-transformed fasting blood glucose (Log [FBS]), body obesity index (BMI), and log-transformed fasting serum insulin that control age, sex, and BMI as covariates in non-diabetic subjects. (Log [insulin]), homeostasis model assessment (HOMA) and regression analysis with waist / hip ratio (WHR) were performed (see Table 9 below).

Table 9. PCK polymorphism and log-transformed fasting blood glucose (Log [FBS]), body obesity index (BMI), log-transformed fasting serum insulin, controlling age, sex and BMI as covariates in non-diabetic subjects (Log [insulin]), homeostasis model assessment (HOMA) and regression analysis with waist / hip ratio (WHR)

(Continued Table 9)

^a C / C, C / R and R / R denote homozygotes for universal alleles and heterozygotes and homozygotes for minor alleles, respectively. Genotype and haplotype distribution (mean ± SD of log-converted fasting blood glucose (mg / dl), BMI (Kg / m ² ), log-converted fasting serum insulin (mg / dl), HOMA, and waist / hip ratio ), And P-values (co-dominant, dominant and recessive models for regression analysis).

As such, in the present invention, one of the haplotype PCK1-ht3 was confirmed to have a sensitive effect on the risk of T2DM (type 2 diabetes mellitus). The genetic association between the mutation / haplotype information and HDL (high density lipoprotein) and TG (triglyceride) identified in the present invention can be usefully used for the study of genetic epidemiology of important genes.

Attach sequence list electronic file  

Claims (3)

Phosphoenolpyruvate Carboxykinase 1 (PCK1) gene for predicting high density lipoprotein and triglyceride levels with gene base mutations, wherein the PCK1 gene base mutation is + 69th from the beginning of translation of the gene PCK1 gene, characterized in that the base is G, the + 1428th base is G, the + 1573th base is C, the + 3404th base is C, the + 4513th base is G and the + 4824th base is C. delete The PCK1 gene of claim 1, for predicting or diagnosing type 2 diabetes by predicting high density lipoprotein and triglyceride levels.

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