Dataset Information

Type 2 Diabetes Susceptibility in the Greek-Cypriot Population: Replication of Associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 Polymorphisms.

ABSTRACT: Type 2 diabetes (T2D) has been the subject of numerous genetic studies in recent years which revealed associations of the disease with a large number of susceptibility loci. We hereby initiate the evaluation of T2D susceptibility loci in the Greek-Cypriot population by performing a replication case-control study. One thousand and eighteen individuals (528 T2D patients, 490 controls) were genotyped at 21 T2D susceptibility loci, using the allelic discrimination method. Statistically significant associations of T2D with five of the tested single nucleotide polymorphisms (SNPs) (TCF7L2 rs7901695, FTO rs8050136, HHEX rs5015480, SLC30A8 rs13266634 and IGF2BP2 rs4402960) were observed in this study population. Furthermore, 14 of the tested SNPs had odds ratios (ORs) in the same direction as the previously published studies, suggesting that these variants can potentially be used in the Greek-Cypriot population for predictive testing of T2D. In conclusion, our findings expand the genetic assessment of T2D susceptibility loci and reconfirm five of the worldwide established loci in a distinct, relatively small, newly investigated population.

SUBMITTER: Votsi C

PROVIDER: S-EPMC5295011 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Type 2 Diabetes Susceptibility in the Greek-Cypriot Population: Replication of Associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 Polymorphisms.

Votsi Christina C Toufexis Costas C Michailidou Kyriaki K Antoniades Athos A Skordis Nicos N Karaolis Minas M Pattichis Constantinos S CS Christodoulou Kyproula K

Genes 20170106 1

Type 2 diabetes (T2D) has been the subject of numerous genetic studies in recent years which revealed associations of the disease with a large number of susceptibility loci. We hereby initiate the evaluation of T2D susceptibility loci in the Greek-Cypriot population by performing a replication case-control study. One thousand and eighteen individuals (528 T2D patients, 490 controls) were genotyped at 21 T2D susceptibility loci, using the allelic discrimination method. Statistically significant a ...[more]

PMID: 28067832

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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: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:IntroductionCurrent study aimed to find the association of genes polymorphism of CDKAL1, HHEX, CDKN2A/2B, and IGF2BP2 with type 2 diabetes (T2DM) in the population of Uttarakhand.Research design and methodsOverall 469 persons comprising 369 recently diagnosed T2DM cases and 100 healthy control were enrolled in the present study. The polymorphisms were analyzed through the PCR-RFLP technique.ResultsFor the rs10440833 variant (CDKAL1), CC genotype's frequency was significantly high among T2DM subjects than controls and increase the T2DM risk (OR: 4.46, 95% CI: 2.22-8.99, p <0.0001). The c allele was significantly found to increase the T2DM risk (OR: 2.20, 95% CI: 1.54-3.14, p <0.001). In the rs1111875 variant (HHEX), the difference of genotype frequencies among T2DM cases and control was statistically non-significant (p-0.138). We did not observe significant differences in allelic frequencies among T2DM cases and control (p-0.444). In the case of rs10811661 variant (CDKN2A/2B), frequency of both TC (OR: 3.16, 95% CI: 1.84-5.42, p <0.0001) and TT (OR: 5.84, 95% CI: 1.75-19.45, p -0.004) genotype were significantly higher in T2DM cases in comparison with control and significantly associated with higher T2DM risk. Compared to the C allele, a significant increase in T2DM risk was documented with the T allele (OR: 2.47, 95% CI: 1.55-3.92, p <0.001). For rs4402960 variant (IGF2BP2), TT genotype contributed to increased T2DM risk (OR: 4.25, 95% CI: 2.02-8.93, p -0.0001). T allele's frequency was significantly high in T2DM cases in comparison with healthy control. Except WHR, HDL-C, exercise, household chores, standing work more than 3 hours, and family history, significant differences were found between T2DM cases and healthy individuals in all other parameters.ConclusionOur study concluded a significant association of CDKAL1, CDKN2A/2B, and IGF2BP2 polymorphism with T2DM in the Uttarakhand population. For HHEX, the genotype and allelic frequencies difference between T2DM cases and control were statistically non-significant. However, a significant association of HHEX gene polymorphism with T2DM was observed only under the dominant model.

Dataset Information

Type 2 Diabetes Susceptibility in the Greek-Cypriot Population: Replication of Associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 Polymorphisms.

Publications

Type 2 Diabetes Susceptibility in the Greek-Cypriot Population: Replication of Associations with TCF7L2, FTO, HHEX, SLC30A8 and IGF2BP2 Polymorphisms.

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