Molecular genetic analysis of CCR2 and CCL2 in age–related macular degeneration

Abstract

Abstract: : Purpose: Mice deficient in monocyte chemoattractant protein–1 (MCP–1, CCL–2) or its C–C chemokine receptor–2 (CCR–2) develop features resembling age–related macular degeneration (AMD). We investigated whether variants of these genes contribute to the disease occurring in humans. Methods: Sporadic cases as well as affected sibpairs with early AMD, geographic atrophy, neovascular AMD and control subjects were ascertained from Dutch clinics. The diagnosis was based on fundus photography using the International Classification System. All coding and flanking intronic regions of CCL–2 and CCR–2 were amplified by PCR and analyzed by DHPLC. Variants were confirmed by direct sequencing. Results: Two intronic variants and two exonic variants were detected in CCL–2. C35C was present in 38/91 cases and 38/86 controls (P=0.11); A71T was present in 1/91 sporadic cases, 1/89 sibpairs, and was not found in 86 controls (P=0.5). Five variants were detected in CCR–2, all in the coding region. There were no differences in CCR–2 allele frequencies between 90 sporadic cases, 97 sibpairs, and 86 controls. Conclusions: Genetic variants of CCL–2 and CCR–2 do not appear to contribute significantly to AMD in humans. Larger cohorts are needed to evaluate the involvement of rare variants.

Keywords: age–related macular degeneration • genetics • gene screening