Assessment Of Interaction Between Smoking And The LOC387715 (ARMS2)/HTRA1 Genes In Risk Of Age-related Macular Degeneration (AMD)

Abstract

Purpose: : To evaluate interaction between smoking and the LOC387715/HTRA1 genes in risk of Age-related Macular Degeneration (AMD) in a large non-clinic based Australian cohort.

Methods: : Nested genetic case-control study of 2294 cases and 2294 controls (matched on age, sex and country of birth from the Melbourne Collaborative Cohort Study aged 48-86 years at follow up (2003-2007). Participant’s smoking habit (never, previous, current) was estimated from a structured interview at baseline in 1990-94. At follow up during 2003-07, digital macula photographs of both eyes were taken and evaluated for signs of early AMD. Genotyping of single nucleotide polymorphisms (SNPs) rs10490924 and rs3793917 in LOC387715 (ARMS2) and rs11200638 in the HTRA1 gene was undertaken. Statistical analysis was performed using logistic regression and likelihood ratio tests in STATA.

Results: : Genotypes were significantly associated with an increased risk of early AMD, odds ratio (OR) (OR 1.47, 95% confidence intervals (95%CI), 1.30, 1.67 and OR 2.86, 95%CI 2.14, 3.82) for one and two copies of the T risk allele respectively for the rs10490924 SNP of LOC387715/ARMS2 and (OR 1.46, 95%CI 1.29, 1.66 and OR 2.05, 95%CI 1.59, 2.64) for one and two copies of the A risk allele respectively for the rs11200638 SNP of the HTRA1 gene, and smoking was significantly associated with early AMD (P=0.04) having adjusted for sex, age, country of birth, educational level, energy intake, waist-to-hip ratio, and known cardiovascular disease or diabetes. However, no significant multiplicative interaction between genotypes and smoking was observed in this cohort (p>0.05).

Conclusions: : These findings support the association of genetic variants at the LOC387715 (ARMS2)/HTRA1 gene region in increased risk of early AMD in a large non clinic based study. This study finds that although smoking is associated with increased risk in AMD, there is no observable gene-environment multiplicative interaction for smoking at this locus. These findings suggest that both risk factors are associated with early AMD independently.

Keywords: age-related macular degeneration • genetics