The association between macular pigment optical density and CFH, ARMS2, C2/BF, and C3 genotype

Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk for this condition may be classified as genetic or environmental, with an interaction between such factors predisposing to this disease. This study investigated the relationship between AMD risk genes, macular pigment optical density (MPOD), which may protect against AMD, and serum concentrations of the macular carotenoids, lutein (L) and zeaxanthin (Z). This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. We also calculated MPOD Area as the area of MP under the spatial profile curve, to reflect MP across the macula. Serum L and Z were measured by HPLC. Genotyping of tag SNPs in the genes CFH, ARMS2, C3, C2 and BF was undertaken with multiplex polymerase chain reaction (PCR) and primer extension methodology (ABI Snapshot, ABI Warrington UK) on DNA extracted from peripheral blood. The mean ± SD (range) age of the subjects in this study was 48 ± 11 (21-66) years. There was a statistically significant association between CFH genotype and family history of AMD, with subjects having two non-risk CFH haplotypes (n = 35), or one non-risk and one protective CFH haplotype (n = 33), being significantly more likely to have a negative family history of AMD (Pearson Chi square: p = 0.001). There was no significant association between the AMD risk genes investigated and either MPOD (One way ANOVA: p > 0.05) or serum concentrations of L or Z (One way ANOVA: p > 0.05, for both). Subjects who were homozygous for risk alleles of both CFH and ARMS2 (n = 4) had significantly lower MPOD at 0.5° and 1° retinal eccentricity (Independent samples t test: p < 0.05) and lower MPOD Area which approached statistical significance (Independent samples t test: p = 0.058), compared to other subjects (n = 291). In conclusion, this study did not detect an association between individual AMD risk genotypes and the putatively protective MP, or serum concentrations of its constituent carotenoids. However, the combination of homozygous risk alleles at both CFH and ARMS2 loci was associated with significantly lower MPOD centrally, despite comparable serum concentrations of the macular carotenoids. These findings suggest that the maculae of subjects at very high genetic risk of AMD represent a hostile environment for accumulation and/or stabilization of MP.