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=3.52x10(-7), 8.35x10(-8), and 7.65x10(-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.