Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disorder, resulting from the
interaction of genetic and environmental factors. This study aimed to assess the association of
TCF7L2 rs12255372 G/T variant with T2DM and insulin resistance (IR) in a sample of the Iraqi
population. A total of 76 patients with T2DM and 54 healthy controls were genotyped for the
TCF7L2 rs7903146 single nucleotide polymorphism (SNP). The association of different
genotypes of this SNP with the development of T2DM as well and with IR and glycated
hemoglobin (HbA1c) were assessed. The TT genotype showed a higher frequency in diabetic
patients (17.11%) than controls (5.56%) with a significant difference (OR = 4.04, 95% CI =
1.04-15.71, p = 0.044). Furthermore, the T allele was more frequent in patients than controls
(38.82% vs. 26.85%), with a significant difference (OR = 1.73, 95% CI = 1.01-2.95, p = 0.45).
Mean HOMA-IR in patients carrying TT genotype was 2.91 ± 0.83 which was significantly
higher than either GG or GT genotype (2.62 ± 0.63 and 2.71 ± 0.55, respectively). Thus, the T
allele of TCF7L2 rs12255372 variant could be considered as a risk factor for developing T2DM.
The study suggests that increase IR is the underlying mechanism by which this variant can
predispose the individual for T2DM.
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