Associations Of SNPs In ARMS2/HTRA1 With Age-related Macular Degeneration

Objectives:To investigate the association between the variants of ARMS2 and HTRA1 gene and the risk of AMD in Ningxia population.Methods:Four hundred and forty-seven patients with AMD and nine hundred and six controls were recruited in Ningxia Eye Hospital form January 2011 to July 2014. All individuals underwent comprehensive eye examinations and genomic DNA was prepared from peripheral blood. The single nucleotide polymorphisms(SNPs) of 13 susceptibility loci in ARMS2/HTRA1 were genotyped. The differences of genotype distribution of allele and haplotype frequencies were compared between patients and controls and the relationship of genotype distribution with AMD was evaluated by using plink. Measures of linkage disequilibrium was carried out by Haploview.Results:All the genotypes met Hardy-Weinberg equilibrium. Six SNPs were found to be different in the genotypic distributions and allele frequencies between patients and normal controls after correction(all at P≤0.05), including the SNPs of rs100490924、rs2248799、rs2253755、rs2736911、rs2736912、rs2736914.The allele distribution of rs10490924 was most significantly associated with AMD(OR=2.599;95%CI=2.180-3.099). In addition, thirteen SNPs were consisted of three blocks after analysis by Haploview. The difference of the TC、GC and GT haplotypes in the first block(rs10490924-rs2736912)were statistical significance between AMD patients and controls(P<0.000).After 100000 permutations, The difference of the AGG haplotypes in thesecond block(rs11200647-rs2753755-rs230043)were statistical significance between AMD patients and controls(P<0.000).Conclusions:The SNPsrs100490924、rs2248799、rs2253755、rs2736911、rs2736912、rs2736914of ARMS2/HTRA1 gene are associated with AMD in Ningxia population. The TC、GC and GT haplotypes of rs10490924 and rs2736912 were significantly associated with AMD.