Elsevier

Ophthalmology

Volume 118, Issue 4, April 2011, Pages 642-648
Ophthalmology

Original article
Genome-wide Association Study of Diabetic Retinopathy in a Taiwanese Population

https://doi.org/10.1016/j.ophtha.2010.07.020Get rights and content

Purpose

Diabetic retinopathy (DR) is a microvascular complication of diabetes with a complex multifactorial pathogenesis. The aim of this study was to identify the susceptibility genes that increase the risk of DR in type 2 diabetes (T2D) and to further elucidate the underlying mechanism of DR pathogenesis.

Design

A case-control study.

Participants

We included 749 unrelated individuals with T2D (174 with DR and 575 without DR) and 100 nondiabetic controls.

Methods

We conducted a genome-wide association study using Illumina HumanHap550-Duo BeadChips.

Main Outcome Measures

Compared with the genotypic distribution of single nucleotide polymorphisms (SNPs) between subjects with DR and without DR.

Results

Using statistical models, we selected a total of 12 SNPs with P-values <1 × 10–6 that were associated with DR. After controlling for diabetes duration and hemoglobin A1C, 9 of the 12 SNPs located on 5 chromosomal regions were found to be associated with DR. Five loci not previously associated with DR susceptibility were identified in and around the following genes: MYSM1 (Myb-like, SWIRM, and MPN domains 1) located on chromosome 1p (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.03–2.20); PLXDC2 (plexin domain-containing 2) located on the chromosome 10p (OR, 1.67; 95% CI, 1.06–2.65); ARHGAP22 (Rho GTPase-activating protein 22) located on chromosome 10q (OR, 1.65; 95% CI, 1.05–2.60); and HS6ST3 (heparan sulfate 6-O-sulfotransferase 3) located on chromosome 13q (OR, 2.33; 95% CI, 1.13–4.77). The SNPs rs13163610 and rs17376456 located in the unknown gene on chromosome 5q were also associated with DR (OR, 3.63; 95% CI, 1.38–9.58).

Conclusions

We identified a genetic association for susceptibility to DR in 5 novel chromosomal regions and PLXDC2 and ARHGAP22, the latter 2 of which are genes implicated in endothelial cell angiogenesis and increased capillary permeability. These findings suggest unsuspected pathways in the pathogenesis of DR.

Financial Disclosures

The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Section snippets

Subjects

The study involved 749 unrelated individuals with T2D over the age of 20 years, who were recruited from the China Medical University Hospital, Taichung, Taiwan. Subjects were diagnosed using the American Diabetic Association Criteria. Subjects with type 1 diabetes, gestational diabetes, or maturity-onset diabetes of the young were excluded from this study. Of this group, 174 T2D subjects were diagnosed with DR: 102 (58.6%) with nonproliferative DR (NPDR) and 72 (41.4%) with proliferative DR

Results

We conducted a genome-wide association study to identify genetic variants for DR in T2D Han Chinese residing in Taiwan. We genotyped 749 T2D patients (174 with DR and 575 without DR) and 100 nondiabetic controls using Illumina HumanHap550-Duo BeadChips. The demographic and clinical characteristics of the previously mentioned groups are summarized in Table 1. Subjects without DR were of a significantly younger age at the time of study and diagnosis and had a shorter disease duration, lower HbA1C

Discussion

Herein, we have described the results of a genome-wide association study designed to identify loci associated with the risk of DR in subjects with T2D. Significant associations were identified in regions of chromosomes 1, 5, 10, and 13 after controlling for diabetes duration and HbA1C levels. The results implicate MYSM1, PLXDC2, ARHGAP22, HS6ST3, and an unknown gene on chromosome 5q as being involved in the pathogenesis of DR, and particularly, with the exception ARHGAP22, in NPDR, although the

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  • Cited by (0)

    Manuscript no. 2010-181.

    Supported by China Medical University Hospital, Taichung, Taiwan (DMR92-076 and DMR93-017), and the National Research Program for Genomic Medicine from National Science Council, Taipei, Taiwan, as well as the National Clinical Core for Genomic Medicine at Academia Sinica, Taipei, Taiwan (NSC96-3112-B-001-010).

    Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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