association of high myopia with crystallin beta a4 (cryba4) gene polymorphisms in the linkage-identified myp6 locus协会的高度近视与晶状体蛋白βa4(cryba4)基因多态性在linkage-identified myp6轨迹.pdf

Association of High Myopia with Crystallin Beta A4 (CRYBA4) Gene Polymorphisms in the Linkage-Identified MYP6 Locus 1,2 2 1,2 2 2 Daniel W. H. Ho , Maurice K. H. Yap , Po Wah Ng , Wai Yan Fung , Shea Ping Yip * 1 Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR, China, 2 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China Abstract Background: Myopia is the most common ocular disorder worldwide and imposes tremendous burden on the society. It is a complex disease. The MYP6 locus at 22 q12 is of particular interest because many studies have detected linkage signals at this interval. The MYP6 locus is likely to contain susceptibility gene(s) for myopia, but none has yet been identified. Methodology/Principal Findings: Two independent subject groups of southern Chinese in Hong Kong participated in the study an initial study using a discovery sample set of 342 cases and 342 controls, and a follow-up study using a replication sample set of 316 cases and 313 controls. Cases with high myopia were defined by spherical equivalent # -8 dioptres and emmetropic controls by spherical equivalent within 61.00 dioptre for both eyes. Manual candidate gene selection from the MYP6 locus was supported by objective in silico prioritization. DNA samples of discovery sample set were genotyped for 178 tagging single nucleotide polymorphisms (SNPs) from 26 genes. For replication, 25 SNPs (tagging or located at predicted transcription factor or microRNA binding sites) from 4 genes were subsequently examined using the replication sample set. Fisher P value was calculated for all SNPs and overall association results were summarized by meta-analysis. Based on