Dataset Information

SLC30A8, CDKAL1, TCF7L2, KCNQ1 and IGF2BP2 are Associated with Type 2 Diabetes Mellitus in Iranian Patients.

ABSTRACT: Background:Type 2 diabetes mellitus (T2DM) is a serious public health issue with significantly increasing rates across the world. The genome-wide association studies (GWAS) have previously manifested involved genes that remarkably enhance the risk of T2DM. In this study, the association of common variants with T2DM risk has been identified among Iranian population from Tehran province of Iran. Methods:Here, the association of refSNPs with T2DM risk was examined on peripheral blood samples of 268 individuals including control group and patients with T2DM using the tetra amplification refractory mutation system (ARMS) methods and direct genomic DNA sequencing. Results:Our study demonstrated that SLC30A8 rs13266634 (T/C), CDKAL1 rs10946398 (A/C), TCF7L2 rs7903146 (C/T), KCNQ1 rs2237892 (T/C), and IGF2BP2 rs1470579 (A/C) polymorphisms are significantly associated with type 2 diabetes, but no significant association was identified for FTO rs8050136 and MTNR1B rs10830963 polymorphisms. Conclusion:The prediction of refSNPs is remarkably needed for pharmacogenetics and pharmacogenomic approaches, in which the information would be useful for clinicians to optimize therapeutic strategies and adverse drug reactions in patients with T2DM.

SUBMITTER: Vatankhah Yazdi K

PROVIDER: S-EPMC7102914 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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<i>SLC30A8, CDKAL1, TCF7L2, KCNQ1</i> and <i>IGF2BP2</i> are Associated with Type 2 Diabetes Mellitus in Iranian Patients.

Vatankhah Yazdi Kazem K Kalantar Seyed Mehdi SM Houshmand Massoud M Rahmanian Masoud M Manaviat Masoud Reza MR Jahani Mohammad Reza MR Kamalidehghan Behnam B Almasi-Hashiani Amir A

Diabetes, metabolic syndrome and obesity : targets and therapy 20200324

<h4>Background</h4>Type 2 diabetes mellitus (T2DM) is a serious public health issue with significantly increasing rates across the world. The genome-wide association studies (GWAS) have previously manifested involved genes that remarkably enhance the risk of T2DM. In this study, the association of common variants with T2DM risk has been identified among Iranian population from Tehran province of Iran.<h4>Methods</h4>Here, the association of refSNPs with T2DM risk was examined on peripheral blood ...[more]

PMID: 32273741

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Project description:BACKGROUND:Several type 2 diabetes (T2D) susceptibility loci identified via genome-wide association studies were found to be replicated among various populations. However, the influence of these loci on T2D in Thai population is unknown. The aim of this study was to investigate the influence of eight single nucleotide polymorphisms (SNPs) reported in GWA studies on T2D and related quantitative traits in Thai population. METHODS:Eight SNPs in or near the KCNQ1, CDKN2A/2B, SLC30A8, HHEX, CDKAL1, TCF7L2, MTNR1B, and UBE2E2 genes were genotyped. A case-control association study comprising 500 Thai patients with T2D and 500 ethnically-matched control subjects was conducted. Associations between SNPs and T2D were examined by logistic regression analysis. The impact of these SNPs on quantitative traits was examined by linear regression among case and control subjects. RESULTS:Five SNPs in KCNQ1 (rs2237892), CDK2A/2B (rs108116610, SLC30A8 (rs13266634), TCF7L2 (rs7903146) and MTNR1B (rs1387153) were found to be marginally associated with risk of developing T2D, with odds ratios ranging from 1.43 to 2.02 (p?=?0.047 to 3.0?×?10-4) with adjustments for age, sex, and body mass index. Interestingly, SNP rs13266634 of SLC30A8 gene reached statistical significance after correcting for multiple testing (p?=?0.0003) (p?<?0.006 after Bonferroni correction). However, no significant association was detected between HHEX (rs1111875), CDKAL1 (rs7756992), or UBE2E2 (rs7612463) and T2D. We also observed association between rs10811661 and both waist circumference and waist-hip ratio (p?=?0.007 and p?=?0.023, respectively). In addition, rs13266634 in SLC30A8 was associated with glycated hemoglobin (p?=?0.018), and rs7903146 in TCF7L2 was associated with high-density lipoprotein cholesterol level (p?=?0.023). CONCLUSION:Of the eight genes included in our analysis, significant association was observed between KCNQ1, CDKN2A/2B, SLC30A8, TCF7L2, and MTNR1B loci and T2D in our Thai study population. Of these, CDKN2A/2B, SLC30A8, and TCF7L2 genes were also significantly associated with anthropometric, glycemic and lipid characteristics. Larger cohort studies and meta-analyses are needed to further confirm the effect of these variants in Thai population.

Project description:Recent advance in genetic studies added the confirmed susceptible loci for type 2 diabetes to eighteen. In this study, we attempt to analyze the independent and joint effect of variants from these loci on type 2 diabetes and clinical phenotypes related to glucose metabolism.Twenty-one single nucleotide polymorphisms (SNPs) from fourteen loci were successfully genotyped in 1,849 subjects with type 2 diabetes and 1,785 subjects with normal glucose regulation. We analyzed the allele and genotype distribution between the cases and controls of these SNPs as well as the joint effects of the susceptible loci on type 2 diabetes risk. The associations between SNPs and type 2 diabetes were examined by logistic regression. The associations between SNPs and quantitative traits were examined by linear regression. The discriminative accuracy of the prediction models was assessed by area under the receiver operating characteristic curves. We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1.406 (P value range from 0.0335 to 1.37E-12). But no significant association was detected between SNPs from WFS1, FTO, JAZF1, TSPAN8-LGR5, THADA, ADAMTS9, NOTCH2-ADAM30 and type 2 diabetes. Analyses on the quantitative traits in the control subjects showed that THADA SNP rs7578597 was association with 2-h insulin during oral glucose tolerance tests (P = 0.0005, empirical P = 0.0090). The joint effect analysis of SNPs from eleven loci showed the individual carrying more risk alleles had a significantly higher risk for type 2 diabetes. And the type 2 diabetes patients with more risk allele tended to have earlier diagnostic ages (P = 0.0006).The current study confirmed the association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes. These type 2 diabetes risk loci contributed to the disease additively.

Dataset Information

SLC30A8, CDKAL1, TCF7L2, KCNQ1 and IGF2BP2 are Associated with Type 2 Diabetes Mellitus in Iranian Patients.

Publications

<i>SLC30A8, CDKAL1, TCF7L2, KCNQ1</i> and <i>IGF2BP2</i> are Associated with Type 2 Diabetes Mellitus in Iranian Patients.

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