Association Study Of ABCA1 Gene And Primary Angle Closure Glaucoma In A Han Chinese Population

Objective: More recently,genetic variants near the ABCA1 gene were reported significantly associated with POAG through genome-wide association studies(GWAS).Previousfindings also suggest that coordinated ABCA1 activity across neurons and glial cells influences neuroinflammation and neurodegeneration.Considering that primary open closure glaucoma(POAG)and primary angle closure glaucoma(PACG)share the common characteristic of opticnerve degeneration and many similar clinical manifestations,the aim of our study was to investigate whether these genetic variants were also associated with PACG in a Han Chinese population.Methods: A case-control association strategy of 1122 cases(PACG/PAC)and 1311 controls was undertaken.Seven single-nucleotide polymorphisms(SNPs)near the ABCA1 gene,including rs2422493,rs2487042,rs2472496,rs2472493,rs2487032,rs2472459,and rs2472519,were genotyped by SNaPshot.Genotype allele frequencies and Hardy-Weinberg equilibrium(HWE)were assessed using X2 tests.Linkage disequilibrium(LD)structure was analyzed by Haploview software.Quantitative data was analyzed by the t test.The Bonferroni correction was used to adjust P values for multiple testing.We applied different statistical models,including dominant and recessive models,to analysis the genotype distributions.We applied Logistic regression to adjust for age gender differences between cases and controls.Finally,we used software(PS;Power and Sample Size Calculation,version 3.1.2)to calculate statistical power.Results:The call rate of all seven SNPs were more than 98%,and their allele distributions were within the HWE for both case and control groups(P> 0.05),with the exception of the HWE of rs2422493,which was slightly deviant in the case(P =0.0012).Among the genotyped SNPs,no association was observed between these SNPs and PACG.To further investigate association between these selected SNPs and PAC/PACG,we used two genetic models.There was no significance difference in two genetic models between PAC/PACGcases and controlsafter adjusting for sex and age and Bonferroni correction.Subsequent comparisons of PAC group and PACG group with control group,respectively;there were no statistically significant differences.Wethenconducted association study of acute and chronic PAC/PACG cases with controls,respectively.None of the SNPs near the ABCA1 gene showed statistically significant differences between chronic or acute PAC/PACG cases and controls.Furtherly,there were no differences in two haplotypes-TATTTACand CGCCCGT-between PAC/PACG cases and controls by haplotype analysis.Conclusions: Our findings suggest that seven SNPnear the ABCA1 Gene(rs2422493,rs2487042,rs2472496,rs2472493,rs2487032,rs2472459,rs2472519)were not statistically associated with PACGin a Han Chinese Population.Thisstudyextendsourunderstanding of the association between ABCA1 gene and glaucoma,and providesinformation for pathogenesis study of glaucoma.