Poster Presentation 9th GeneMappers Conference 2012

Investigating association between the FOXO3A gene and Age-Related Macular Degeneration (AMD) (#107)

Andrea J Richardson 1 , Madeleine K Adams , Julie A Simpson 2 , Khin Zaw Aung 1 , Galina A Makeyeva 1 , Dallas R English 2 3 , Luba D Robman 1 , Graham Giles 3 , John Hopper 2 , Robyn H Guymer 1 , Paul N Baird 1
  1. Centre for Eye Research Australia, East Melbourne, VIC, Australia
  2. Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Melbourne School of Population Health, University of Melbourne, Victoria, Australia
  3. Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia


Age-related macular degeneration (AMD) affects the elderly and is the leading cause of blindness in the western world, where smoking and ageing are two known major risk factors.  We hypothesized that elderly cohorts could be enriched with protective genotypes of genes associated with longevity which may ultimately influence survival.  We used a tag-single nucleotide polymorphism (tag-SNP) approach to investigate genetic associations of the polymorphism of the longevity FOXO3A gene (chromosome 6q21).


2,294 AMD cases and 2,294 controls were selected from the Melbourne Collaborative Cohort Study (MCCS) (age range 48-86 years), of which 116 cases had late stage AMD.  Genotyping was performed on the MassArray platform (Sequenom, San Diego, CA).  Ten tag-SNPs were tested (r2 >0.8, minor allele frequency (MAF) of 0.05).  Genotype frequencies were compared across 5-year age intervals.  Logistic regression, adjusted for age, sex and smoking was performed using Stata version 10.


Polymorphisms (minor alleles) in the SNPs rs13207511 (p=0.009), rs2253310 (p=0.02) and rs7747393 (p=0.03) were significantly associated with early AMD.  Genotype frequencies for the tag-SNP rs13207511 were also associated with smoking status with the minor homozygote genotype frequency increasing by 4% in current smokers (with no sign of early AMD).  None of the SNPs were associated with AMD late.  No significant differences were observed in genotype frequencies across the different age groups for any of the tag-SNPs in either AMD or controls.


The FOXO3A gene was weakly associated with early AMD and smoking in the cohort but not with late AMD in this cohort.  As elderly smokers with no signs of macular degeneration were more likely to be in possession of one or more minor FOXO3 alleles, enrichment with these alleles could signify protection against degenerative changes, thus influencing survival.  No association of FOXO3A was evident with longevity which may reflect the lack of extremely old individuals in this cohort.