Susceptible Genes And Its Interaction With Environmental Factors On Exudative Age-related Macular Degeneration In Chinese Population

Purpose:To assess the genotypic distribution of single neucleotide polymorphisms (SNPs) in CFH,BF and HTRA1 genes and their association with exudative AMD susceptibility in Han Chinese population.The interaction between environmental factors and genes were also evaluated.Methods:A case-control study with age,gender and ethnicity matched was conducted to genotype the representative SNPs loci including rs1061170 and rs1410996 in CFH,rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP,and the relationships between SNPs and AMD were explored.The environmental factors for AMD and the interaction between environmental factors and CFH and HTRA1 genes were analyzed by multivariate unconditional logistic regression.Results:The C risk allele frequencies for CFH rs1061170(Y402H) in case and control groups were 12.5%and 5.4%respectively,which were much lower than those in Caucasian(P＜0.001).Y402H polymorphism was moderately associated with AMD susceptibility(OR=2.63,1.36-5.07).In contrast to homozygous genotype of non-risk allele,the heterozygous genotype of risk allele was positively associated with AMD with odds ratio of 3.23(1.36-5.07).However,no association was found between the homozyous genotype of risk allele and exdutative AMD(probably because the frequency in Chinese population is too low to detect the association in our study).The population attribute risk(PAR) of C risk allele was only 3.3%(1.4-4.3%).Rs1410996 was also associated with AMD independent of Y402H.The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.24 fold (1.04-4.79) and 3.93 fold(1.74-8.87) respectively,with correspondent PARs of 28.3% (2.0-40.5%) and 38.2%(21.8-45.4%).Rs641153 in BF was not associated with AMD (OR 0.66(0.40-1.09)),and no polymorphism of Rs4151667 in BF was found in Han Chinese population.Rs11200638 in HTRA1 was a susceptible locus for AMD with odds ratio of 2.24(1.57-3.20):although the heterozygous genotype was not associated with AMD,homozygotes of risk alleles were significantly susceptible for exedutie AMD(OR=3.98,1.88-8.43) with PAR of 38.9%(24.3-45.8%).Three variables,namely smoking status,education status and egg intake were included in the final model using multiple logistic regression with stepwise backwards method.Ever smoking was a strong risk factor for AMD(OR=6.60,2.21-19.72),while high education status and high egg intake were found to be protective factors for AMD with OR of 0.17 (0.08-0.37) and 0.33(0.14-0.79) respectively.The analysis of interaction between gene and environmental factors suggests:smoking synergisticly increased susceptibility of AMD for heterozygotes of intronic SNP rs1410996,with OR_interaction of 11.42(P_interaction =0.029).Other environmental factors and genotypes were all independent of AMD.Conclusion:In Han Chinese population,CFH Y402H variant is associated with exudative AMD,although the genotype distribution is significantly different from Caucasian.It is possible that other susceptibility loci in CFH are associated with AMD. The promoter polymorphism in HTRA1 gene is a stronger genetic susceptible locus of exudative AMD than CFH Y402H in Chinese population.R32Q and L9H variants in BF are not associated with AMD,which contradicts previous investigations in Caucasians.Various environmental factors are associated with AMD,and susceptible genes and environmental factors attribute independently to AMD.No interactions between selected genes are found,while sigarette smoking,a modifiable environmental factor,is interactive with genetic susceptible genes.