Single-nucleotide polymorphisms in chromosome 3p14.1- 3p14.2 are associated with susceptibility of Type 2 diabetes with cataract

PURPOSE: Type 2 diabetes (T2D) is highly prevalent worldwide and cataracts are of high incidence in T2D patients. In this study, we identify genetic variants that predispose type 2 diabetes (T2D) patients to cataracts in the Han-Chinese residing in Taiwan. METHODS: We conducted a genome-wide association study with a total of 1,715 cases and 2,000 random controls. In the haplotype study, we defined haplotype 1 (Ht 1) to haplotype 4 (Ht 4) as the alternative alleles of the DM and cataract related chromosome 3p14.1- 3p14.2 polymorphisms. RESULTS: The most significant association was detected with rs11129182, rs17047573, and rs17047586 in chromosome 3p14.1- 3p14.2 (p value=3.52×10(−7), 8.35×10(−8), and 7.65×10(−8), respectively). In genotype analysis, the “CT” genotype of rs11129182, the ‘GG’ genotype of rs17047573, and the ‘GG’ genotype of rs17047586 were significantly different in the T2D and cataract groups (OR=3.03, 7.47, and 7.51, individually; 95% confidence index (CI): 1.97–4.65, 3.36–16.6, and 3.38–16.7, individually). In the haplotype study, the distribution of the Ht3 and Ht4 between the DM and cataract group and the control group differed significantly between the two groups (p=0.0004). The odds ratio (OR) of Ht4 was 1.89 and the 95% confidence interval (CI) was 1.36–2.65. CONCLUSIONS: The major functions of the genes are voltage-dependent anion-selective channel proteins, long myosin light chain kinase, adenylyl cyclase-associated proteins and retinoic acid receptors and are all closely related with the pathogenesis of T2D and cataractogenesis. This has helped us understand the pathogenesis of T2D patients with cataracts.