FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians

Aims and hypothesis  Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune. Methods  We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India. Results  We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13–1.40; p = 3 × 10⁻⁵). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01–0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09–0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06–1.37; p = 4.0 × 10⁻³), and also for waist circumference and other anthropometric variables. Conclusions  Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. C. S. Janipalli, S. Bhaskar, S. R. Kulkarni and R. M. Freathy contributed equally to this study.     

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China

Aims/hypothesis  Two recent genome-wide association studies have identified several novel type 2 diabetes susceptibility variants in intron 15 of the KCNQ1 gene. We aimed to evaluate the effects of the variants in KCNQ1 on type 2 diabetes and metabolic traits in the population of mainland China. Methods  Three candidate single nucleotide polymorphisms were genotyped in 1,912 individuals with type 2 diabetes and 2,041 normal controls using the ligase detection reaction method. Results  We confirmed the association of KCNQ1 with type 2 diabetes in the population of mainland China. Allele frequency ORs of the three single nucleotide polymorphisms (SNPs) were: rs2237892 (OR 1.19, 95% CI 1.08–1.31, p = 3.0 × 10⁻⁴); rs2237895 (OR 1.20, 95% CI 1.09–1.32, p = 1.9 × 10⁻⁴); and rs2237897 (OR 1.24, 95% CI 1.13–1.36, p = 3.9 × 10⁻⁵). We also found a significant difference in the distribution of the global haplotypes between the type 2 diabetes group and the normal control group (p = 2.6 × 10⁻⁵). In addition, in the control group SNP rs2237892 was marginally associated with increasing fasting plasma glucose and SNPs rs2237892 and rs2237897 were associated with HbA_1c. Furthermore, for all three variants, homozygous carriers of the diabetes-associated allele had significantly decreased BMI and waist circumferences. Conclusions/interpretation  Our investigation confirmed the effects of KCNQ1 variants on type 2 diabetes risk in the Chinese population. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. Y. Liu and D. Z. Zhou contributed equally to this study.     

转录因子7类似物2基因rs11196205多态性与安徽地区2型糖尿病及糖调节受损的相关性

目的 探讨转录因子7类似物2(TCF7L2)基因rs11196205位点多态性在安徽地区汉族人群中与2型糖尿病(T2DM)和糖调节受损(IGR)的相关性.方法 选取2009年1月至8月于安徽医科大学第一附属医院就诊的2型糖尿病患者300例、糖调节受损患者300例和糖耐量正常对照者(NGT)300名,收集临床资料和采集血样,测定生化指标并提取DNA;探针固定于芯片,PCR制备荧光标记靶基因与芯片杂交,扫描杂交结果;采用单因素方差分析及K-W检验统计分析rs11196205突变等位基因和基因型频率与T2DM及IGR发病的关系.结果 TCF7L2基因rs11196205位点等位基因频率[C在T2DM、IGR、NGT组频率分别为21%(126/600)、19%(114/600)、11%(68/600)]和基因型频率[GC+CC在T2DM、IGR、NGT组频率分别为41%(122/300)、37%(111/300)、22%(67/300)].T2DM与NGT、IGR与NGT、T2DM+IGR与NGT 3组比较差异均有统计学意义(P<0.05).携带突变等位基因C可增加罹患T2DM(OR=2.08,95%C1=1.51～2.86,X2=20.68,P<0.05)、IGR(OR=1.84,95%CI=1.33～2.54,X2=13.71,P<0.05)或任何一种(OR=1.96,95%CI=1.46～2.61,X2=21.18,P<0.05)的风险.与野生纯合基因型GG比较,体内携带一个以上突变基因C复本可增加罹患T2DM(OR:2.38,95%CI=1.67～3.40,X2=23.37,P<0.05)、IGR(OR=2.04,95%CI=1.43～2.92,X2=15.46,P<0.05)或任何一种(OR=2.21,95%CI=1.61～3.03,X2=24.50,P<0.05)的风险.结论 rs11196205位点G→C突变在安徽地区汉族人群中可能与T2DM和IGR关联,携带突变等位基因C可显著增加罹患T2DM和IGR的风险.     

2型糖尿病精氨酸刺激后胰岛素原的释放及其与血糖的关系

目的探讨2型糖尿病(T2DM)患者精氨酸刺激后胰岛素原(PI)释放的变化及其与血糖水平的关系。方法选择2001年11月至2003年8月上海交通大学附属第六人民医院的106例T2DM患者及35名正常糖耐量(NGT)健康对照者行精氨酸刺激试验,分析比较精氨酸刺激试验后PI及其增值(ΔPI)和PI/[真胰岛素(TI) PI]的变化。结果(1)T2DM组精氨酸刺激后各时间点PI、PI/(TI PI)值显著高于NGT组(P均<0.01),其PI在2min时达峰值,随后呈逐渐下降趋势。(2)不同空腹血糖(FPG)的T2DM患者各时间点PI、PI/(TI PI)分析显示FPG2组(7mmol/L≤FPG<9mmol/L)和FPG3组(FPG≥9mmol/L)明显高于FPG1组(FPG<7mmol/L,P均<0.05)。结论精氨酸刺激后PI“不成比例”增加是T2DM患者胰岛B细胞功能缺陷的重要表现之一,因此在比较T2DM与NGT人群胰岛B细胞功能时应测定TI以减少PI的干扰。     

Transcription factor 7-like 2 (TCF7L2) gene polymorphism rs7903146 is associated with stroke in type 2 diabetes patients with long disease duration

Associations between TCF7L2 SNP and diabetic complications and diabetes-related factors were investigated. Subjects with rs7903146 variant had significantly higher prevalence of stroke (24.1% vs. 11.1%; P = 0.039) among subjects exhibiting a long disease duration (≥10 years). In conclusion, the TCF7L2 SNP variant may confer a higher risk of stroke in diabetic patients.     

The association of the common fat mass and obesity associated gene polymorphisms with type 2 diabetes in obese Iraqi population

Background & objectivesThis study investigates the association of two potential Fat mass and obesity associated gene (FTO) gene polymorphisms (rs9939609 and rs918031) as potential predictors of type 2 diabetes (T2D) in obese Iraqi population and their metabolic effects on hyperglycemia and insulin sensitivity.Materials & methodsThe study included 400 participants with obesity & T2D, with a matching 400 obese non-diabetic cohort. Venous blood samples were collected for DNA extraction. Using specific primers and restriction enzymes, genotyping was performed to identify the various alleles for each gene. The genotype and allele frequencies determined by multinomial logistic regression analysis for FTO single nucleotide polymorphisms (rs9939609) among all the study groups.ResultsThere is a two-fold increase in the risk of T2D within the homozygous genotype (TT) group (OR = 2.43, CI 95% 3.57–11.2, P ≤ 0.001) as compared to the wild type (TA). In addition, there was a significantly higher level of the minor allele genotype (T) in T2D patients when compared to the control group, (P ≤ 0.001).ConclusionWe conclude that the FTO rs9939609 genotype significantly affect the development of insulin resistance, therefore the future occurrence of T2D, in obese individuals.