Identification of Diabetic Retinopathy Genes through a Genome-Wide Association Study among Mexican-Americans from Starr County, Texas

Author:

Fu Yi-Ping1,Hallman D. Michael1,Gonzalez Victor H.2,Klein Barbara E. K.3,Klein Ronald3,Hayes M. Geoffrey4,Cox Nancy J.5,Bell Graeme I.5,Hanis Craig L.1

Affiliation:

1. Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, P.O. Box 20186, Houston, TX 77225, USA

2. Valley Retina Institute, McAllen, TX 78503, USA

3. Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA

4. Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

5. Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA

Abstract

To identify genetic loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas, completed physical examinations including fundus photography for diabetic retinopathy grading. Individuals with moderate-to-severe non-proliferative and proliferative diabetic retinopathy were defined as cases. Direct genotyping was performed using the Affymetrix GeneChip Human Mapping 100 K Set, and SNPs passing quality control criteria were used to impute markers available in HapMap Phase III Mexican population (MXL) in Los Angeles, California. Two directly genotyped markers were associated with severe diabetic retinopathy at aP-value less than .0001: SNP rs2300782 (P=6.04×105) mapped to an intron region of CAMK4 (calcium/calmodulin-dependent protein kinase IV) on chromosome 5, and SNP rs10519765 (P=6.21×105) on chromosomal 15q13 in the FMN1 (formin 1) gene. Using well-imputed markers based on the HapMap III Mexican population, we identified an additional 32 SNPs located in 11 chromosomal regions with nominal association with severe diabetic retinopathy atP-value less than .0001. None of these markers were located in traditional candidate genes for diabetic retinopathy or diabetes itself. However, these signals implicate genes involved in inflammation, oxidative stress and cell adhesion for the development and progression of diabetic retinopathy.

Publisher

Hindawi Limited

Subject

Ophthalmology

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