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 a P-value less than .0001: SNP rs2300782 (P = 6.04 × 10(-5)) mapped to an intron region of CAMK4 (
calcium/calmodulin-dependent protein kinase IV) on chromosome 5, and SNP rs10519765 (P = 6.21 × 10(-5)) 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 at P-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.