Purpose
It is well established that the Y402H CFH polymorphism increases risk for AMD. Previous research shows that high versus low vitamin D status, assessed with serum concentrations of 25-hydroxyvitamin D [25(OH)D], is associated with decreased odds of AMD. Whether the vitamin D association is modified by genetic risk for AMD remains to be examined.
Methods
Using data from the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women’s Health Initiative, we examined whether the association between serum [25(OH)D] and AMD was modified by presence of the CFH Y402H polymorphism. There were 1,230 postmenopausal women aged 50-79 at study baseline (1994-98) with complete genotype data and available serum samples. [25(OH)D] were assessed at baseline by competitive chemiluminescence immunoassay. Prevalent AMD (n=249) was assessed six years later by stereoscopic fundus photographs. Logistic regression was used to estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early or late AMD by [25(OH)D] (<30, 30 to <50, ≥50 to <75, and ≥75 nmol/L) and CFH Y402H genotype (noncarrier, one risk allele, two risk alleles). The referent group was Y402H noncarriers with inadequate vitamin D status (<30 nmol/L).
Results
Among women with inadequate ([25(OH)D]<30 nmol/L) or adequate ([25(OH)D]>75 nmol/L) vitamin D status, having two risk alleles was associated with an increased odds of AMD but the odds was attenuated in those adequate vitamin D status (OR=4.30, 95% CI=1.21-15.20 and OR=1.56, 95% CI=0.54, 4.52, respectively). Among noncarriers and women with one risk allele, the odds of AMD was decreased in women with [25(OH)D]>75 (OR=0.82, 95% CI=0.29-2.33 and OR=0.89, 95% CI=0.34-2.35, respectively). In women with 2 risk alleles, having [25(OH)D]>75 lowered the odds for AMD 64% (OR=1.56, 95% CI=0.54, 4.52) relative to those with [25(OH)D]<30 (OR=4.30, 95% CI=1.21-15.20). The P for interaction between vitamin D status and genotype was 0.35. Further adjustment for use of hormone therapy, sunlight exposure and eye color did not alter the associations.
Conclusions
In this sample of postmenopausal women, the odds of AMD decreased with increasing [25(OH)D] across all genotypes, but most markedly among those with two risk alleles for the CFH Y402H genotype.
Keywords: 412 age-related macular degeneration •
539 genetics •
464 clinical (human) or epidemiologic studies: risk factor assessment