LOC387715/HTRA1 polymorphisms, smoking and combined effects on exudative age-related macular degeneration in a Korean...

This study was to investigate the association of two single nucleotide polymorphisms (SNPs) in LOC387715 and HTRA1 with exudative age-related macular degeneration (AMD) in a Korean population and the gene-gene and gene-environment interactions in the development of AMD.

We genotyped two SNPs that are located in the LOC387715 locus (rs10490924) and HTRA1 (rs11200638) in 137 cases of exudative AMD and 187 controls.

Both two SNPs were significantly associated with AMD (P = 0.0001). Homozygotes for the risk allele at LOC387715 and HTRA1 had a 3.80-fold and a 4.03-fold increased risk of exudative AMD, respectively, compared with homozygotes for the wild-type allele (P = 0.0001). The joint effects for complement factor H (CFH) Y402H and 10q26 variants indicated an increased risk of exudative AMD. The odds ratios (ORs) of AMD for individuals carrying one-, two- and three-copy risk alleles of CFH Y402H and LOC387715 were 1.08, 3.49 and 3.64, respectively. Also, the combination effect of the CFH Y402H risk alleles with HTRA1 risk alleles was dose-dependent. The interaction analysis between gene and environmental factors showed that among several factors, smoking synergistically increased the susceptibility of AMD for variants of LOC387715 and HTRA1, with OR 8.33 (3.05-22.74) and OR 8.50 (3.07-23.51), respectively.

This study demonstrated the significant association of the 10q26 SNPs (HTRA1 and LOC387715) in an AMD cohort from Korea and was consistent with previous studies from other populations. Also, a statistically significant interaction between genetic and environmental factors was found.