Purpose: To investigate the effect of single nucleotide polymorphisms (SNPs) and haplotypes in the genes encoding age-related maculopathy susceptibility 2 (LOC387715/ARMS2) and high-temperature requirement A-1 (HTRA1) in a case-control study in a Chinese cohort of individuals with exudative age-related macular degeneration (AMD).
Methods: We genotyped 2 SNPs, namely, LOC387715 rs10490924 and HTRA1 rs11200638, in 159 exudative AMD patients and 140 age- and sex-matched control subjects. All the four possible haplotypes of these two SNPs were detected. Comparisons of the risk genotypes and risk or protective haplotypes across multiple populations were performed.
Results: Allelic or genotype association tests yielded significant results at P < 0.001. We observed that homozygous risk genotypes (TT in rs10490924 and AA in rs11200638) were more strongly associated with AMD than the heterozygous genotypes (GT in rs10490924 and geographic atrophy in rs11200638) for both SNPs. Comparisons of the odds ratios for genotypes revealed that there is ethnic disparity in AMD prevalence, even within the Chinese population. The haplotype TA, comprising both the SNPs, was identified as an at-risk factor and was significantly associated with AMD, whereas the protective haplotype GG was significantly overrepresented in the controls (P < 0.001). The frequency of the TA haplotype was relatively higher in the Chinese population than in the white population in both groups, whereas the frequency of the GG haplotype was relatively lower in the Chinese controls than in the white and Japanese controls.
Conclusion: Both SNPs are significantly associated with exudative AMD in the Chinese cohort and seem to contribute equally to the disease status. A higher frequency of homozygous risk genotypes and risk haplotype and a lower frequency of protective haplotype in the Chinese may be the cause of higher prevalence of exudative AMD in the Chinese than in the whites.