Dataset Information

Association of genetic polymorphism of PC-1 gene (rs1044498 Lys121Gln) with insulin-resistant type 2 diabetes mellitus in Punjabi Population of Pakistan.

ABSTRACT: BACKGROUND:Insulin resistance (IR), known to reduce the response to insulin action, develops with obesity leading to type 2 diabetes mellitus (T2DM). The PC-1 gene has been associated with dyslipidemia, polycystic ovarian disease and T2DM in different regions of the world. The objective of the present study was to investigate the genetic association of PC-1 rs1044498 polymorphism with insulin resistance in type 2 diabetes in the Punjabi population of Pakistan. METHODS:This study was carried out on 161 healthy controls and 161 patients of T2DM with insulin resistance. Whole blood was collected for DNA extraction and molecular studies. PCR-RFLP with AvaII was performed to determine the genotype in cases and controls. Chi-square and Hardy Weinberg analyses were carried out. Statistical analysis was performed by SPSS software. RESULTS:The demographic data of cases and controls showed significant differences for different parameters like glucose, insulin, Homeostatic model assessment-insulin resistance (HOMA-IR) and lipid profiles (p < 0.000). Different statistical models revealed that all the dominant models were found associated in between alleles for disease risk (p < 0.001) while no association of PC-1 rs1044498 (K121Q) polymorphism was found with insulin-resistant parameters in T2DM cases. CONCLUSION:Overall, the results indicate that the K121Q polymorphism was not found associated with insulin resistance in type 2 diabetes in a Pakistani Punjabi population. This is the first-ever report about the genotype of PC-1 gene in this population.

SUBMITTER: Albegali AA

PROVIDER: S-EPMC6687647 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Association of genetic polymorphism of PC-1 gene (rs1044498 Lys121Gln) with insulin-resistant type 2 diabetes mellitus in Punjabi Population of Pakistan.

Albegali Abdullah Abdo AA Shahzad Muhammad M Ullah Muhammad Ikram MI Mahmood Saqib S Rashid Maryam M

Molecular genetics & genomic medicine 20190628 8

<h4>Background</h4>Insulin resistance (IR), known to reduce the response to insulin action, develops with obesity leading to type 2 diabetes mellitus (T2DM). The PC-1 gene has been associated with dyslipidemia, polycystic ovarian disease and T2DM in different regions of the world. The objective of the present study was to investigate the genetic association of PC-1 rs1044498 polymorphism with insulin resistance in type 2 diabetes in the Punjabi population of Pakistan.<h4>Methods</h4>This study w ...[more]

PMID: 31250990

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Project description:Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T > C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk. Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models). Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082-1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095-5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055-2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148-3.257, p = 0.013) with random effects model. After omitting Gouda's study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004-1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model. Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.

Project description:BACKGROUND AND AIMS:Genetic variants involved in vitamin D metabolism have been associated with diabetes and related syndromes/diseases. We wanted to investigate possible associations of polymorphisms in genes involved in vitamin D metabolism with indices of insulin resistance and insulin secretion, and also with development of diabetes after gestational diabetes mellitus (GDM). MATERIALS AND METHODS:We have studied 376 women with previous GDM. Eight single nucleotide polymorphisms (SNPs) in the genes for vitamin D receptor (VDR) [rs731236, rs7975232, rs10735810, and rs1544410], vitamin D binding protein (DBP) [rs7041 and rs4588], and cytochrome P450 family 27 subfamily B member 1 (CYP27B1) [rs10877012 and rs4646536] were genotyped by TaqMan Allelic Discrimination Assay using the Quantstudio 7 Flex system. A 75-g oral glucose tolerance test (OGTT) was performed 1-2 years postpartum. The homeostasis model assessment of insulin resistance (HOMA-IR) and the disposition index [(insulinogenic index: I30/G30)/HOMA-IR] were used to calculate insulin resistance and insulin secretion, respectively. Serum samples for determination of 25(OH)D3 were collected at the time of the OGTT. Manifestation of diabetes was followed up to five years postpartum. RESULTS:After adjustment for BMI, age, and ethnicity, the A-allele of the VDR rs1544410 polymorphism was found to be associated with increased disposition index (difference per allele = 3.56, 95% CI: 0.4567-6.674; p = 0.03). The A-allele of the DBP rs7041 polymorphism was found to be associated with 25(OH)D3 levels (difference [in nmol/L] per allele = -5.478, 95% CI: -8.315 to -2.641; p = 0.0002), as was the T-allele of the DBP rs4588 polymorphism (OR = -6.319, 95% CI: -9.466 to -3.171; p = 0.0001). None of the SNPs were significantly associated with HOMA-IR or postpartum diabetes. CONCLUSIONS:This study provides evidence that the rs1544410 polymorphism of the VDR gene may be associated with increased insulin secretion in women after pregnancy complicated by GDM. Further studies in other populations are needed to confirm the results.

Dataset Information

Association of genetic polymorphism of PC-1 gene (rs1044498 Lys121Gln) with insulin-resistant type 2 diabetes mellitus in Punjabi Population of Pakistan.

Publications

Association of genetic polymorphism of PC-1 gene (rs1044498 Lys121Gln) with insulin-resistant type 2 diabetes mellitus in Punjabi Population of Pakistan.

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