Abstract
To study associations between type 2 diabetes (T2DM) candidate genes and microvascular complications of diabetes (MVCDs), we performed case-control association studies for both T2DM and MVCDs in Han Chinese subjects. We recruited 1,939 unrelated Han Chinese T2DM patients and 918 individuals with normal blood glucose levels as nondiabetic controls. Among T2DM patients, 1116 have MVCDs, 266 have a history of T2DM of >10 years but never developed MVCDs. Eighty-two single-nucleotide polymorphisms (SNPs) in 54 candidate genes were genotyped. Discrete association studies were performed by the PLINK program for T2DM and MVCDs. Significant associations were found among candidate gene SNPs and T2DM, including rs1526167 of the TOX gene (allele A, P = 2.85 × 10−9, OR = 1.44). The SNP rs10811661 of the CDKN2A/B gene was also associated with T2DM (allele T, P = 4.09 × 10−7, OR = 1.36). When we used control patients with >10 years of T2DM history without MVCD, we found that the G allele of SNP rs1526167 of the TOX gene was associated with MVCD (nominal P = 4.33 × 10−4). In our study, significant associations were found between TOX and CDKN2A/B gene SNPs and T2DM. The TOX polymorphism might account for the higher risk of T2DM and the lower risk of MVCDs in the Han Chinese population.
Highlights
The prevalence of type 2 diabetes (T2DM) has increased dramatically in China in recent years[1,2]
In microvascular complications of diabetes (MVCDs) association studies, Diabetic nephropathy (DN), diabetic retinopathy (DR), proliferative retinopathy (PDR), and MVCD patients were selected as cases, and patients with >10 years T2DM history, without DR or DN, were chosen as controls
Association analyses of dichotomous variables showed that rs1526167 of the TOX gene was associated with DN (P = 0.0011, odds ratios (ORs) = 1.470, 95% confidence intervals (CIs) = 1.166–1.854), DR (P = 0.0082, OR = 1.412, 95% CI = 1.093– 1.825), and MVCD (P = 4.33 × 10−4, OR = 1 .498, 95% CI = 1 .195–1.878)
Summary
The prevalence of type 2 diabetes (T2DM) has increased dramatically in China in recent years[1,2]. With the remarkable rise worldwide in the prevalence of diabetes, an increase in patients suffering from microvascular complications of diabetes (MVCDs) will be inevitable. Previous studies have shown that the duration of diabetes and plasma glucose levels are MVCD risk factors[7,8], some diabetes patients with severe hyperglycemia never develop MVCDs. In contrast, many diabetes patients with well-controlled blood glucose suffer from MVCDs9. Many association studies have identified genes related to MVCDs15, the search for MVCD susceptibility genes was less successful than for T2DM susceptibility genes, partially because of un-diagnosed MVCDs and lack of appropriate normal controls. We aimed to find T2DM and MVCD candidate genes in Han Chinese T2DM patients by studying associations between single-nucleotide polymorphisms (SNPs) of candidate genes and T2DM/ MVCDs
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