| Objective: 1. The associations among genetic variants in VEGFR1 and a predisposition to age-related macular degeneration(AMD) along with potential environmental contribution in Ning Xia region were evaluated; 2. Investigating whether there are the associations between VEGFR1 genetic variants along with smoking exposure and the risk of AMD in Hui and Han ethnics in the Ning Xia population; 3. Delving into whether there are the links between VEGFR1 SNPs and AMD among neovascularization and early-middle stage.Methods: A case-control correlation study was conducted on 432 cases including 325 ethnic Han and 107 ethnic Hui, with 139 early-middle and 287 neovascular AMD subjects, and 906 gender-and ethnicity-matched controls containing 698 ethnic Han and 208 ethnic Hui. Uniform questionnaires were administered to obtain baseline information and exposure information of related factors, such as history of smoking, hypertension and diabetes apart from name, age and gender. The whole DNA was isolated from peripheral blood sample after the individuals underwent detailed eye examinations. Eight Tag single nucleotide polymorphisms(t SNPs) in VEGFR1 genes were genotyped for all individuals using a MALDI-TOF technique. Using SPSS 17.5 and Plink for Windows software package established databank. Non-conditional Logistic regression was performed to screen the risk factors. The distributions of genotypes were analyzed for Hardy-Weinberg equilibrium and the relationships among the genotype and allele frequencies with AMD were evaluated by Logistic regression analysis with adjusted odds ratios(ORs) and their accompanying 95% confidence intervals(CIs) among varied genetic models. Bonferroni testing was employed to correct for multiple comparisons. The measurement of linkage disequilibrium(LD) and haplotype blocks based on LD were carried out by Haploview 4.2, and haplotypes were corrected by using permutation test after running 50,000 times.In addition, Non-conditional Logistic regression was performed to analyze for the relationships among the genotype and allele frequencies between VEGFR1 SNPs and Han and Hui population with AMD along with neovascular and early-middle stage AMD, respectively. Meanwhile, adjusted odds ratio and 95% confidence interval were evaluated.Results:1. Smoking(OR=2.147, 95%CI=1.556~2.943), and hypertension(OR=2.388, 95%CI=1.871~3.048) are risk factors for AMD by single and multiple Logistic methods(P< 0.05). Among the SNPs genotyped, P values of six SNPs were less than 0.05 between AMD cases and unaffected controls. However, after Bonferroni correction, the genotype and allele distributions of only two SNPs, rs9554322 and rs9582036 differed significantly between the controls and AMD patients(P <0.0062). Further, the rs9554322 CC genotype conferred strong susceptibility to AMD(OR=6.057, 95%CI: 3.099–11.839). Rs9943922 was also found to be significantly associated with AMD in the distributions for the genotype and allele recessive model(P=0.004). The specific haplotype CA of rs9582036 and rs9554320 was associated with AMD(P=0.035), but the correlation did not remain after correction.2. In the Hui and Han Chinese case groups, the frequencies of alleles showed no statistical significance(P> 0.05). Rs9554322 and rs9582036 SNPs were found to be significantly different in the genotypic distributions and allele frequencies between patients and controls in the Han population(P=0.000, P=0.006) after Bonferroni correction, and the odds ratio and 95% confidence interval values in allele distributions were 1.671(1.234-2.262) and 1.477(1.124-1.940), respectively, whereas significant difference was detected in genotype distribution of rs9943922 between AMD and controls in the Han population(P=0.001). Rs9554322 was merely identified as significant difference in the genotypic distributions and allele frequencies between patients and controls in the Hui population(P=0.000, P=0.000). Statistically, the exposure to smoke consumption was likely to augment the AMD risk in the Han people(P=0.000, OR=2.622, 95%CI: 1.899-3.619) rather than in Hui(P=0.198).3. Rs9554322 SNP was found to be significantly different in the genotypic distributions and allele frequencies between patients and controls in early-middle and neovascular AMD, and the odds ratio and 95% confidence interval values in allele distributions were 2.181(1.476-3.222) and 1.838(1.376-2.454), respectively. Furthermore, rs9582036 differed significantly between the controls and AMD patients.Conclusions:1. Smoking and hypertension may independently increase the risk of AMD. The SNPs rs9554322, rs9582036 and rs9943922 were correlated with AMD. Gene variants in VEGFR1 were linked to a pronounced emerging risk for AMD in Ning Xia area.2. Of the eight SNPs tagged, the genotypes and alleles of rs9554322, rs9582036 and rs9943922 seemed to confer susceptibility to AMD in ethnic Han, and the risk for AMD may increase in Hui individuals only for rs9554322. Smoking was the independent risk component for Han population with AMD.3. Rs9554322 may link to AMD onset among different stages, whereas only rs9582036 to neovascular in Ningxia Area. |
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