Y402H Variant in Complement Factor H (CFH): Association with Age-Related Maculopathy (ARM) and Correlation with Macular Pigment Optical Density (MPOD), Serum C-Reactive Protein (CRP), and Lutein & Zeaxanthin (L&Z) in a Mid-South US Elderly Sample

Abstract

Purpose: : To report on the association between the Y402H CFH variant and ARM in Mid-South US elderly participants in the Health ABC ARM Ancillary (ARMA) Study, and to investigate the correlation between this genotype, MPOD, serum CRP and L&Z.

Methods: : The rs1061170 SNP was genotyped with Taqman Assays on Demand (Applied Biosystems). Of the 340 ARMA Study participants (all >70 years old, 81% White; total ARM: n=110; AREDS cat. 3: n=86; cat. ≥4: n=24), genotype information could be obtained in 303 of them, and in 104 of the ARM cases. Serum L&Z were measured by HPLC methods, CRP by high sensitivity methods, and both were log-transformed.

Results: : The high-risk allele for SNP rs1061170 was observed in 41.4% of the sample, and in homozygosity in 55 subjects (18.2%). The resulting Y402H variant was associated with increased ARM odds in White subjects (age and sex-adj. OR=2.15, 95% CI 1.17 to 3.95). The Black ARM sub-sample was too small to verify the association. MPOD and serum measurements were available for 150 of the unaffected and 68 of the ARM genotyped subjects. Ln(CRP) serum levels tended to be higher by genotype (YY: 0.66±1.24 µg/mL; YH: 0.82±1.16 µg/mL; HH: 1.15±1.23 µg/mL; p=0.07), but there was no difference in either MPOD or serum ln(L&Z) levels. The expected positive L&Z-MPOD relationship was not affected by CFH genotype, whereas the CRP-L&Z correlation was opposite between YY (inverse) and HH subjects (direct).

Conclusions: : Higher odds of ARM associated with the Y402H CFH change were seen also in this Mid-South sample with mainly early (AREDS cat. 3) ARM. Homozygosity for the HH variant tended to be associated with a higher inflammatory load by CRP criteria. Carrying the H variant did not affect the retinal MPOD-L&Z relationship, suggesting that higher L&Z intakes via diet or supplements would achieve MPOD augmentation not only regardless of disease status (Iannaccone et al. IOVS 2007;48: E-Abs. 2147) but also regardless of CFH genotype. The expected inverse CRP-L&Z correlation (Kritchevsky et al. AJE 2000; 152: 1065-71) was seen only in participants with the YY (wild-type) genotype.

Keywords: age-related macular degeneration • genetics • inflammation