Ethnic Differences In Htra1/arms2 Association In Age-related Macular Degeneration

Abstract

Purpose: : Age-Related Macular Degeneration (AMD) is one of the most common causes of visual impairment among the aging population in the United States. Individuals of African American descent have a lower AMD risk, but the reasons for this difference are unknown. We tested known risk alleles associated with AMD in individuals of African and European descent.

Methods: : A case-control data set of 2,012 Caucasians and 67 African-Americans was ascertained from the Vanderbilt Center for Human Genetics Research, the John P. Hussman Institute for Human Genomics, and the University of Tennessee Health Sciences Center. Smoking history and genotyping at rs1061170 (CFH Y402H), rs10490924 (ARMS2 A69S), rs2230199 (C3 R102G), mtDNA 4917, rs641153 (CFB R32Q) and 32 loci spanning HTRA1/ARMS2 were analyzed. Affection status for Caucasian (AMD=1,192, Ctrl=820) and African American (AMD=16, Ctrl=51) individuals was based on the more severely affected eye. Multivariate analysis was carried out in each population, controlling for age of exam, smoking, and gender.

Results: : In Caucasians, the risk alleles at rs1061170 (p=2.95 x 10 ^-23, Odds Ratio (OR) =2.10), rs10490924 (p=2.08 x 10^-22, OR=2.13) and the protective allele at rs641153 (p=7.04 x 10^-12, OR=0.39) were significantly associated with AMD. In the African-American sample, none of these were significant. Only rs2672590 (near HTRA1/ARMS2, p=0.03, OR=2.78) was marginally significant in African-Americans, but had the opposite effect in Caucasians (p=8.79 x 10^-5, OR=0.70).

Conclusions: : Despite minimal power, HTRA1/ARMS2 intergenic SNP rs2672590 was marginally significantly associated with AMD in African Americans. The opposite effect observed in Caucasians suggests that the mechanism of action for the HTRA1/ARMS2 locus may be ancestry-specific.

Keywords: age-related macular degeneration