Dataset Information

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population.

ABSTRACT: BACKGROUND:The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. METHODS:The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-? were used to measure insulin resistance and ?-cell secretory function, respectively. RESULTS:The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired ?-cell function. CONCLUSION:In the Russian population, genes, which affect insulin synthesis and secretion in the ?-cells of the pancreas, play a central role in the development of T2DM.

SUBMITTER: Nikitin AG

PROVIDER: S-EPMC5511504 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association of polymorphic markers of genes <i>FTO</i>, <i>KCNJ11, CDKAL1, SLC30A8,</i> and <i>CDKN2B</i> with type 2 diabetes mellitus in the Russian population.

Nikitin Aleksey G AG Potapov Viktor Y VY Brovkina Olga I OI Koksharova Ekaterina O EO Khodyrev Dmitry S DS Philippov Yury I YI Michurova Marina S MS Shamkhalova Minara S MS Vikulova Olga K OK Smetanina Svetlana A SA Suplotova Lyudmila A LA Kononenko Irina V IV Kalashnikov Viktor Y VY Smirnova Olga M OM Mayorov Alexander Y AY Nosikov Valery V VV Averyanov Alexander V AV Shestakova Marina V MV

PeerJ 20170713

<h4>Background</h4>The association of type 2 diabetes mellitus (T2DM) with the <i>KCNJ11, CDKAL1, SLC30A8, CDKN2B,</i> and <i>FTO</i> genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes.<h4>Methods</h4>The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMa ...[more]

PMID: 28717589

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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.

Project description:BackgroundType 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) are two deadly diseases caused by the complex interaction of multiple genetic loci, lifestyle and environmental factors. Genome-wide association studies described hundreds of susceptibility loci for T2DM and T2DM-related CVD, but it remains uncertain due to geographic and ethnic variations. The objective of this study was to evaluate the associations of KCNJ11 rs5219, SLC30A8 rs13266634 and HHEX rs1111875 polymorphisms with T2DM and related CVD.MethodsGenotyping of all three polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method on 250 T2DM cases and 246 healthy controls. Both descriptive and inferential statistical methods were applied using MedCalc and IBM SPSS software programs for statistical analyses.ResultsA significantly increased association of KCNJ11 rs5219 (p<0.05) with T2DM was found in dominant, recessive, heterozygote, homozygote, and allele model (aOR = 2.23, 2.03, 1.90, 3.09, and 1.80, respectively). For SLC30A8 rs13266634, only dominant, heterozygote, and allele model (aOR = 3.37, 3.59, and 1.79, respectively) showed significantly increased association with T2DM. SNP rs1111875 (HHEX) also revealed 2.08, 4.18, 5.93, and 2.08-times significant association in dominant, recessive, homozygote, and allele models. Besides, a significantly reduced correlation of KCNJ11 rs5219 was found with T2DM-related CVD in the recessive and allele model (aOR = 0.40 and 0.65, respectively). Again, a significant difference was observed between T2DM-related CVD and non-CVD patients in terms of gender distribution, fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and triglycerides (TG).ConclusionsOur investigation indicates that KCNJ11 rs5219, SLC30A8 rs13266634 and HHEX rs1111875 polymorphisms are associated with T2DM. Moreover, KCNJ11 rs5219 polymorphism is correlated with the risk of T2DM-related CVD.

Dataset Information

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population.

Publications

Association of polymorphic markers of genes <i>FTO</i>, <i>KCNJ11, CDKAL1, SLC30A8,</i> and <i>CDKN2B</i> with type 2 diabetes mellitus in the Russian population.

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