| Objective:The International AMD Genomics Consortium（IAMDGC）and other research teams discovered a high correlation between LIPC and age-related macular degeneration by Genome Wide Association Studies（GWAS）and case-control study.Choroidal neovascularization（CNV）is a common phenotype for aging macular degeneration in Asian population,especially in China.The research aim to investigate the association between choroidal neovascularization（CNV）and the LIPC gene single nucleotide polymorphism（SNP）in a Han Chinese population from Shantou,includes rs10468017,rs2043085,rs920915,rs493258 and rs2070895.Methods:A case-control study was conducted in 221 patients with CNV who met the diagnostic criteria and 200 healthy controls with age,gender and race matching in shantou international eye center.Peripheral blood DNA were extracted and amplified,the LIPC rs10468017,rs2043085,rs920915,rs493258 and rs207089 were genotyped by SNaPshot method.Sanger sequencing was used to verify the genotyping results.The chi-square test was used to analyze whether the gene frequency and genotype frequency of each SNP conform to Hardy Weinberg equilibrium（HWZ）,P>0.05 indicates that the population has reached the genetic equilibrium.Binary Logistic regression was used to analyze the correlation between the gene frequency of five SNP loci and CNV,P<0.05 was considered statistically significant.In order to further explore the relationship between LIPC and CNV,grouping analysis and stratification analysis were used for correlation analysis of the above five SNP sites.The Bonferroni method was used to correct the P values for multiple comparisons.Haploview software was used to analyze the linkage disequilibrium and haplotype of alleles at the above five loci.Results:1.The genotype rate of the five SNP loci in this study was above99.8%,The results were consistent with those obtained by Sanger sequencing.The five loci of LIPC gene in healthy control group were consistent with Hardy-Weinberg equilibrium（P>0.05）,except rs2043085.2.The risk of LIPC rs493258 in the dominant mode was 0.47 times higher than that the control group（95%CI:0.32-0.70 P=0.000）.The correlation between other loci and CNV in the two genetic models was not statistically significant.3.The gene frequency of the minor allele C of LIPC gene rs493258 in CNV was 0.290,which was lower than that in healthy control（0.410）.The difference was statistically significant（P=0.000,P=0.001 after multiple correction）,and the OR value was 0.59,95%CI（0.44-0.78）.There were no statistically significant differences in the gene frequencies of the minor allele T of LIPC gene rs10468017,C of rs2043085,C of rs920915 and A of rs2070895 in CNV and healthy controls.The P values were 0.955,0.719,0.339 and 0.081,respectively.The OR is0.99（0.70-1.41）,1.05（0.80-1.38）,0.86（0.62-1.18）and 0.79（0.59-1.03）,respectively.4.Grouping analysis results showed that the gene frequency of rs493258minimum allele C in CNV of male subjects was 0.276,which was lower than 0.385in healthy control group,and the difference was statistically significant（P=0.005,P=0.05 after multiple correction）.Stratification analysis results showed that there were no statistically significant differences in the gene frequencies of the minimum allele T（rs10468017）,the minimum allele C（rs2043085）,the minimum allele C（rs920915）and the minimum allele A（rs2070895）in CNV between the LIPC gene SNP locus and the healthy control group.5.LIPC genes rs10468017 and rs2043085,rs493258 and s920915 were in a linkage disequilibrium,with D’is 0.943,0.888 and 0.89,respectively,95%CI is0.85-0.98,0.5-0.97 and 0.69-0.97,respectively.LIPC genes rs493258 and rs920915 were also in a linkage disequilibrium,D’=0.68（95%CI:0.53-0.8）.The linkage disequilibrium between rs10468017 and rs2043085 was the strongest.6.Seven haplotypes of CCTG,CTTG,TTTG,CCTC,CTTC,CCCC and CTCC could be formed by rs10468017,rs2043085,rs493258 and rs920915.The differences of two haplotypes（CCCC and CTCC）in CNV group and control group were statistically significant,with P values of 1.512×10-44 and 7.0×10-4,OR value was 0.75（0.51-0.99）and 0.78（0.41-0.86）respectively.Conclusion:1.The results of this study showed that LIPC rs493258 was associated with choroidal neovascularization caused by wet age-related macular degeneration in this han population from Shantou,LIPC rs493258 was a protective factor of CNV.The correlation between this site and CNV was correlated with gender,but no correlation between this site and CNV was detected in female subjects.There was no significant correlation between rs10468017,rs2043085,rs920915 or rs207089 and choroidal neovascularization caused by wet age-related macular degeneration in this han population from Shantou.2.In this Han population from Shantou,LIPC gene rs10468017 and rs2043085 rs493258,rs920915 are in a state of linkage disequilibrium,and its haplotype（CCCC and CTCC）is a protective factor for angiogenesis of elderly macular degeneration... |
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