Yako Yandiswa Y, Madubedube Jabulisile H, Kengne Andre P, Erasmus Rajiv T, Pillay Tahir S, Matsha Tandi E
Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, South Africa.
Department of Biomedical Sciences Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa.
Afr Health Sci. 2015 Dec;15(4):1149-60. doi: 10.4314/ahs.v15i4.14.
Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations.
To assess the association of these genes with T2DM risk in a South African mixed-ancestry population.
Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits.
In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals.
Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.
转录因子7样2基因（TCF7L2）、脂肪量与肥胖相关基因（FTO）以及外核苷酸焦磷酸酶/磷酸二酯酶基因（ENPP1）是已知的2型糖尿病（T2DM）风险基因座，主要存在于欧洲人群中。
评估这些基因与南非混合血统人群T2DM风险的关联。
采用Taqman基因分型检测法对566名参与者进行ENPP1的rs997509和rs1044498、FTO的9941349和rs3751812、TCF7L2的rs12255372和rs7903146多态性基因分型，并通过自动测序进行验证，以评估这些多态性与心脏代谢特征的关联。
在根据年龄、性别、体重指数（BMI）和胰岛素抵抗进行调整的逻辑回归模型中，rs997509的次要等位基因在隐性模型下与T2DM患病率较高相关[比值比4.60（95%置信区间：1.07至19.86）；p = 0.040]。在加性模型下，rs7903146[1.43（1.00至2.04）；p = 0.053]和rs9941349[1.43（1.00至2.04）；p = 0.052]的次要等位基因与T2DM高风险呈边缘显著关联。然而，只有rs7903146的等位基因（p = 0.011）和基因型（p = 0.025）分布在糖尿病患者和非糖尿病患者之间存在统计学显著差异。
我们的研究结果表明，ENPP1、TCF7L2和FTO可能使混合血统人群易患T2DM。
