Associations Between Variants in Loc387715, Smoking and Age- Related Macular Degeneration in the Eureye Study

Abstract

Purpose: : Previous studies have reported associations between age- related macular degeneration (AMD) and a variant in LOC387715 (rs 10490924). Studies are inconsistent as to whether the associations differ by smoking history. We investigated this in the EUREYE study

Methods: : Participants underwent fundus imaging, were interviewed for risk factors including smoking and provided a blood sample. Images were graded at an independent centre (Rotterdam). All participants gave written, informed consent. Ethics approval was given in each study centre. Stored DNA was available on 560 early and 142 late AMD cases and 614 randomly selected controls frequency matched with cases by age, sex and centre. DNA was genotyped for rs 10490924 and rs4146894 using KASPar technology. We used multinomial logistic regression (Relative Risk Ratios-RRs) adjusted for age and sex and included a smoking x allele interaction term.

Results: : For rs10490924 the control T allele frequency was 35.5% of whom 3.6% were homozygous There were a significant (p=0.01) interaction with smoking and rs10490924 on AMD risk. For early AMD, the RRs (95% CI’s) for never smokers were GT:1.40 (1.12-1.77), p=0.004, TT: 2.15 (1.35-3.40), p<0.001. and for ever smokers GT:1.71 (1.39-2.09) p <0.0001 and TT:4.18 (2.11-8.29) p<0.0001. For late AMD the corresponding risks in never smokers was GT: 3.45 2.43-4.90), p=4.6 x10^-12and TT: 7.45(3.48-15.93), p=2.2x10^-7and ever smokers GT:3.11(1.59-6.10),p<0.001,TT:14.79(6.12-32.0),p=6.4x10^-10.rs4146894 was weakly associated with AMD and not associated when rs 10490924 was added to the model.

Conclusions: : Smoking modified the association with rs10490924 and AMD.

Keywords: age-related macular degeneration • genetics • candidate gene analysis