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

• Published in: Molecular vision 2010-07, Vol.16, p.1206-1214
• Main Authors: Lin, Hui-Ju, Huang, Yu-Chuen, Lin, Jane-Ming, Wu, Jer-Yuarn, Chen, Liuh-An, Lin, Chao-Jen, Tsui, Yung-Ping, Chen, Chih-Ping, Tsai, Fuu-Jen
• Format: Article
• Language: English
• Subjects: Adult; Aged; Case-Control Studies; Cataract - classification; Cataract - complications; Cataract - genetics; Cataracts; chromosome 3; Chromosomes, Human, Pair 3 - genetics; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Female; Gene polymorphism; Genetic Predisposition to Disease; Haplotypes; Haplotypes - genetics; Humans; Male; Middle Aged; Myopia - complications; Myopia - genetics; Myosin-light-chain kinase; Odds Ratio; Polymorphism, Single Nucleotide - genetics; Retinoic acid receptors; Single-nucleotide polymorphism; Vision; Young Adult
• ISSN: 1090-0535; 1090-0535

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. 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. 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. 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.