An Investigation of Selected Candidate Genes for Five-Year Incidence of Age-Related Maculopathy (ARM)in Older Women

Abstract

Purpose: : To investigate the relationship between selected candidate genes and incidence of ARM in a prospective five-year follow-up study.

Methods: : Vision examination and 45°stereoscopic fundus photographs were performed on women who attended two consecutive clinic visits (year 10 and year 15) of the Study of Osteoporotic Fractures (SOF), (a multi-center prospective study of osteoporosis in women aged 65 years and above). DNA was extracted from blood blotters collected from Caucasian women at baseline examination of SOF in 1986, and analyzed for a selection of Single Nucleotide Polymorphisms (SNPs) relevant to bone disease. ARM was determined based on grading of fundus photographs in three progressively ordered groups - absent, early and late. Fisher's exact tests were done to assess the association of genotype of each selected SNP with incident early and late ARM. Logistic regression analyses were performed after adjusting for age and smoking. Associations were examined individually, and no corrections for multiple comparisons were performed.

Results: : Of 1,765 subjects (mean age at baseline 78.8±3.2y, range 74 to 92 y), 1136 women had no ARM at first visit. 151 developed early and 86 women developed late ARM by second visit. Among 43 SNPs analyzed, statistically significant associations were found for Fibrinogen Beta Poly peptide (FBP) (p=0.0155) and Interleukin 6 (IL6) (p=0.0033) polymorphisms with incident early ARM using Fisher's tests. Prolactin (PRL) polymorphism was significantly associated with incident late ARM (p=0.0366). In a G allele recessive genotype model, Interleukin 6 remained significant after adjusting for age and smoking status (p=0.0009).

Conclusions: : The results suggest an association between SNPs on the FBP and IL6 genes with incident early ARM and between PRL and incident late ARM. These findings must be interpreted with caution as associations noted in incident early ARM are not replicated in incident late ARM, nor was there association between PRL and incident early ARM. However, early and late ARM may be mediated by different pathways.

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