Abstract
Hepatocyte nuclear factor 1β (HNF1β), a transcription factor encoded by the transcription factor 2 gene (TCF2), plays a critical role in pancreatic cell formation and glucose homeostasis. It has been suggested that single nucleotide polymorphisms (SNPs) of TCF2 are associated with susceptibility to type 2 diabetes (T2D). However, published results are inconsistent and inclusive. To further investigate the role of these common variants, we examined the association of TCF2 polymorphisms with the risk of T2D in a Han population in northeastern China. We genotyped five SNPs in 624 T2D patients and 630 healthy controls by using a SNaPshot method, and evaluated the T2D risk conferred by individual SNPs and haplotypes. In the single-locus analysis, we found that rs752010, rs4430796 and rs7501939 showed allelic differences between T2D patients and healthy controls, with an OR of 1.26 (95% CI 1.08–1.51, P = 0.003), an OR of 1.23 (95% CI 1.06–1.55, P = 0.001) and an OR of 1.28 (95% CI 1.10–1.61, P = 0.001), respectively. Genotype association analysis of each locus also revealed that the homozygous carriers of the at-risk allele had a significant increased T2D risk compared to homozygous carriers of the other allele (OR 1.78, 95% CI 1.20–2.64 for rs752010; OR 1.82, 95% CI 1.24–2.67 for rs4430796; OR 1.95, 95% CI 1.31–2.90 for rs7501939), even after Bonferroni correction for multiple comparisons. Besides, the haplotype-based analysis demonstrated that AGT in block rs752010-rs4430796-rs7501939 was associated with about 30% increase in T2D risk (OR 1.31, 95% CI 1.09–1.57, P = 0.01). Our findings suggested that TCF2 variants may be involved in T2D risk in a Han population of northeastern China. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.
Highlights
The exact etiology is unknown, type 2 diabetes (T2D) is characterized by dysfunction of pancreatic beta cells and insulin resistance, resulting from the complex interactions of multiple genetic variants and environmental factors including diet, exercise, stress, and medical treatment [1,2]
An interesting observation is that specific variants in the transcription factor 2 gene (TCF2) gene have been identified to be associated with both the risk of prostate cancer [4,5,6] and the risk of T2D [4,7] with the effects being in the opposite direction for these two phenotypes
Subject Characteristics The subjects including 624 T2D patients and 630 non-diabetic controls were genotyped for five representative TCF2 single nucleotide polymorphisms (SNPs) and analyzed for association with T2D
Summary
The exact etiology is unknown, type 2 diabetes (T2D) is characterized by dysfunction of pancreatic beta cells and insulin resistance, resulting from the complex interactions of multiple genetic variants and environmental factors including diet, exercise, stress, and medical treatment [1,2]. HNF1b is a POU (Pit-1Oct-1/2-UNC-86) domain transcription factor closely related to HNF1a. Both are expressed in the pancreas, liver, and kidney [8,9]. One Chinese study using a southern population observed the risk G allele of rs4430796 was significantly associated with T2D [20]. Another Caucasian analysis using the subjects from Sweden and Finland could not replicate the association of TCF2 loci with future risk of T2D in two prospective studies [21]. In the present study, we conducted a case-control study to investigate the role of TCF2 SNPs on T2D risk in a Han population in northeastern China
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