| Purpose: To investigate the role of the APOE gene polymorphisms(-419A＞T, -427T＞C, -219T＞G,ε2/ε3/ε4)in POAG and AMD, and their interactive effects with the CFH gene polymorphisms(rs3753394, rs800292, rs1329428, rs1061170, rs1061147, rs380390)in AMD.Methods: A cohort of Taiwan Chinese including 94 HTG patiems, 48 NTG patients and 77 control subjects was recruited from the Eye Clinic of Veterans General Hospital, Taiwan. A cohort of Hong Kong Chinese was recruited, including 152 AMD patients and 241 control subjects, from the Eye Clinic of Prince of Wales Hospital, Hong Kong. The three promoter polymorphisms of APOE gene were genotyped by direct sequencing in both cohorts. Theε2/ε3/ε4 polymorphism in the exon-4 of APOE gene was genotyped by restriction fragment length polymorphism(RFLP)and polyacrylamide gel electrophoresis(PAGE)in the Taiwan cohort while the same polymorphism and all the CFH gene polymorphisms were detected with TaqMan SNP Genotyping assays in the Hong Kong cohort. Chi-Square test was used to assess the associations of the APOE gene and CFH gene polymorphisms with POAG and AMD. Logistic regression analysis and Multifactor Dimensionality Reduction(MDR)were used to search for gene-gene interactions between the APOE gene and the CFH gene.Results: In Taiwan cohort, the frequency of allele A at -491A＞T was 98.4％, 97.9％and 97.4％in HTG, NTG and control, respectively. No TT genotype was detected in any group. The T allele frequency of-427T＞C in HTG, NTG and control group was 91.9％, 95.7％and 92.9％, respectively. The CC genotype was only detected in HTG patients(1.1％). The frequency of allele T of -219T＞G was 69.9％, 75.5％and 70.1％in HTG, NTG and control, respectively. Theε3 was the most predominant allele in HTG, NTG and control group(79.8％, 82.3％and 83.8％, respectively). Both theε2 allele(6.9％, 4.2％and 7.1％, respectively)and theε4 allele(13.3％, 13.5％and 9.1％, respectively)had much less frequencies in the three group. No association was detected in the four APOE polymorphisms with POAG in Taiwan Chinese. In Hong Kong cohort, the frequency of allele A of -491A＞T was 96.0％in AMD cases and 97.3％in controls. The allele frequency of -219T was 64.3％in AMD cases and 66.2％in controls. There was no statistically significant association between either -491A＞T or -219T＞G with AMD. Significant association was detected at the genotype frequency of -427T＞C of the APOE gene(P=0.044)and a marginal association was detected at the allele frequency of the same polymorphism(P=0.051). There was statistical significance between AMD and control subjects when comparing the TC genotype to the TT genotype(wild type)of-427T＞C polymorphism(P=0.013). The TC genotype conferred an OR of 2.072(95％CI, 1.159-3.704)for AMD. When subjects with TC genotype and those with CC genotype were pooled together and compared to those with the TT genotype, the P value was 0.024 and the OR was 1.842(95%％CI, 1.077-3.150). Theε2,ε3, andε4 allele frequency was 10.5％, 82.9％and 6.6％in AMD cases and was 9.3％, 82.4％and 8.3％in control subjects, respectively. No association was found between exon 4 polymorphism and AMD, either. None of the APOE polymorphisms had association with either earlier or later diagnostic age of AMD in the Hong Kong cohort. The genotyping results of CFH gene in Hong Kong was described elsewhere. There was no gene-gene interaction between the APOE gene and the CFH gene in AMD in our study.Conclusions: The APOE gene polymorphisms were not associated with POAG in Taiwan Chinese while in Hong Hong Chinese only the -427T＞C polymorphism was associated with AMD. The TC genotype seemed to be a risk factor of AMD in Hong Kong Chinese. There is no evidence of APOE gene and CFH gene interaction in AMD. The roles of the polymorphisms of APOE gene in are yet to be confirmed in both POAG and AMD. |
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