The Association of the LOC387715 Gene and High-Temperature Requirement Protein A1 (HTRA1) Gene With Age-Related Macular Degeneration

Abstract

Purpose: : To determine if the LOC387715 (G>T; Ala69Ser) and HTRA1 (G>A) single nucleotide polymorphisms (SNPs) are associated with wet and dry AMD in a diverse Southern Californian population.

Methods: : Total DNA was isolated from 103 AMD subjects and 126 age-matched control subjects. The LOC387715 and HTRA1 genes were amplified by polymerase chain reaction and digested with PvuII and SfiI, respectively, in order to determine the presence or absence of certain SNPs in these genes. The SISA statistical analyses program was used to quantitatively describe associations between the variable alleles and the AMD and/or control groups.

Results: : Upon examination of the G>T (Ala69Ser) SNP in LOC387715 exon 1, the GG genotype was protective against wet AMD (OR=.345; 95% confidence interval (CI) [.189-.6309]; p=0.00022). Additionally, the GT genotype was associated with wet AMD (OR=1.891; 95% CI [1.072-3.334]; p=0.010), while the TT genotype was associated with both wet and dry AMD (wet: OR=2.522; 95% CI [1.024-6.213]; p=0.023); (dry: OR=3.611; 95% CI [1.087-11.996], p=0.034). Upon examination of the G>A SNP in the promoter region of HTRA1, the GG wild type variant was protective against wet AMD (OR=.393; 95% CI [.216-.715]; p=.0009), while possession of one A allele was found to be associated with wet AMD (OR=2.0; 95% CI [1.13-3.540]; p=.0066).

Conclusions: : The T allele of the LOC387715 (rs10490924) is strongly associated with both the wet and dry forms of AMD, while the HTRA1 polymorphism (rs11200638) is associated only with the wet form of AMD. Our findings support previous studies and demonstrate that AMD likely involves multiple genes.

Keywords: age-related macular degeneration • genetics • detection