Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa|
Yako, Yandiswa Y.; Madubedube, Jabulisile H.; Kengne, Andre P.; Erasmus, Rajiv T.; Pillay, Tahir S. & Matsha, Tandi E.
Background: 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
Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population.
Methods: 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.
Results: 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.
Conclusion: Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry
Type 2 diabetes; genetics; ENPP1; TCF7L2; FTO; Africa