Rivera et al. (2005) identified the T allele of a single-nucleotide polymorphism (SNP) in the LOC387715 gene, rs10490924, as the most likely susceptibility allele for age-related macular degeneration (ARMD8; 613778), accounting for linkage to the chromosome 10q26 region. The G-to-T transversion in exon 1 gives rise to an ala-to-ser substitution at codon 69 (A69S). The study of Schmidt et al. (2006) concluded that variant genotypes at this SNP confer a substantially larger risk of ARMD in smokers than in nonsmokers. The data suggested that the T allele may only moderately increase risk of ARMD in nonsmokers and exerts its strongest effect in heavy smokers.
Maller et al. (2006) confirmed the association of the A69S SNP studied by Rivera et al. (2005) and Schmidt et al. (2006) with ARMD, strongly implicating this variant as causally related to ARMD.
Kanda et al. (2007) determined that rs10490924 in the LOC387715 gene alone, or a variant in strong linkage disequilibrium, could explain the bulk of the association between the 10q26 region and ARMD.
In a matched sample set from the Age-Related Eye Disease Study (AREDS) cohort involving 424 patients with ARMD and 215 patients without ARMD acting as controls, Bergeron-Sawitzke et al. (2009) confirmed association between ARMD and rs10490924, with both the GT (OR, 3.1; p = 1.1 x 10(-8)) and TT (OR, 9.2; p = 4.2 x 10(-9)) genotypes. Bergeron-Sawitzke et al. (2009) noted that rs10490924 is in strong linkage disequilibrium with the rs11200638 SNP (602194.0001) in the promoter region of the HTRA1 gene that has also been associated with ARMD (see ARMD7; 610149).
In a study of 2,167 individuals with the ARMS2 A69S mutation or the CFH Y402H mutation (134370.0008), Ho et al. (2011) found that high dietary intake of nutrients with antioxidant properties reduced the risk of early ARMD.
Fritsche et al. (2013) identified association of the T allele of rs10490924 with increased risk of ARMD (OR 2.76, 95% CI 2.72-2.80, combined p = 4 x 10(-540)).
