Novel susceptibility genes associated with diabetic cataract in a Taiwanese population

Abstract

Purpose: To identify genetic variants that predispose to type 2 diabetes (T2D) with cataract.

Patients and methods: Genome-wide association study (GWAS) of T2D patients with cataract, as graded by Lens Opacities Classification System (LOCS). A total of 109 T2D patients with cataract score equal to or above 10 designated as the study group, 649 T2D patients with cataract score equal to or below 3 as the control group. Single nucleotide polymorphisms (SNPs) with p-values < 10^–5 were considered to be putatively associated with the diabetic cataract.

Results: Fifteen SNPs were found to be putatively associated with diabetic cataract. These variants were located near the following genes: PPARD, CCDC102A, GBA3, NEDD9, GABRR1/2, RPS6KA2, tcag7.1163, TAC1, GALNTL1 and KIAA1671. We defined haplotype 1 to haplotype 4 from the alternative alleles of related polymorphisms. Distribution of haplotype 2 on chromosome 4 and haplotype 4 on chromosome 7 revealed significant differences (OR = 1.86 and 1.69, respectively; 95% confidence interval were 1.26–2.76 and 1.23–2.31, respectively).

Conclusions: The 15 loci coded on chromosomes 4, 6, 7, 14, 16 and 22 were associated with diabetic cataract. Gene functions are either with mechanisms of regulating blood sugar or formation of cataract. High linkage disequilibrium appeared on chromosome 4p15.31 and chromosome 7q21.3.

Keywords::

• Cataract
• diabetic
• genome-wide association study
• haplotype
• linkage disequilibrium

ACKNOWLEDGMENTS

We gratefully acknowledge Emily Hsieh and Chia Ming Wu from the Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan for helping with the experiment. We also acknowledge the National Research Program for Genomic Medicine from the National Science Council, Taiwan, and the National Clinical Core for Genomic Medicine at Academia Sinica for providing support for the statistical analysis, data coordination, subject recruitment, and project management.

Funding sources: This study was supported by the National Research Program for Genomic Medicine from the National Science Council, Taiwan, and the National Clinical Core for Genomic Medicine at Academia Sinica (grant number:NSC96-3112-B-001-010) for providing support (services). We are also grateful for the support from the National Science Council Taiwan (NSC 99-2314-B-039-011-MY3) and the grants from the China Medical University (CMU-95–141, CMU-96–081 and CMU-96-036, Taichung, Taiwan) and China Medical University Hospital (DMR-96–068, DMR-98–076, DMR-99–093, DMR-100-097 and DMR-101-074, Taichung, Taiwan).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.