title: Evaluation of proteoglycan gene polymorphisms as risk factors in the genetic susceptibility to high myopia.
abstract: PURPOSE. To investigate the relationship between high myopia and single nucleotide polymorphisms (SNPs) in six proteoglycan genes: aggrecan (ACAN), fibromodulin (FMOD), decorin (DCN), lumican (LUM), keratocan (KERA), and epiphycan (EPYC). These genes were selected for study because they are involved in induced myopia in animals and/or are within the human MYP3 locus identified by linkage analysis of families with high myopia. METHODS. Two groups of Chinese subjects were studied: group 1 (300 cases and 300 controls) and group 2 (356 cases and 354 controls). Cases were high myopes with spherical equivalent (SE) ≤ -8.00 D, and controls had SE between +1.0 and -1.0 D. From these candidate genes, 60 tagging SNPs were selected. First, 12 DNA pools were each constructed from 50 samples of the same phenotype from group 1 subjects and were tested for association with the SNPs. Second, putatively positive SNPs were confirmed by individual genotyping of group 1 subjects. Finally, positive results were replicated in group 2 subjects. RESULTS. Of the 58 SNPs successfully screened by DNA pooling, 8 ACAN SNPs passed the threshold of P ≤ 0.10 (nested ANOVA) and were then genotyped in the individual samples. Haplotypes rs3784757 and rs1516794 showed significant association with high myopia. However, the positive result could not be replicated in the second subject group. CONCLUSIONS. These six proteoglycan genes were not associated with high myopia in these Chinese subjects and hence are unlikely to be important in the genetic predisposition to high myopia.
authors: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, China. sheaping.yip@inet.polyu.edu.hk
authors: Shea Ping
authors: SP
authors: Yip
authors: Kim Hung
authors: KH
authors: Leung
authors: Po Wah
authors: PW
authors: Ng
authors: Wai Yan
authors: WY
authors: Fung
authors: Pak Chung
authors: PC
authors: Sham
authors: Maurice K H
authors: MK
authors: Yap
mesh_terms: D000328:Adult; D053674:Aggrecans / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D004252:DNA Mutational Analysis; D058575:Decorin / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D000071235:Fibromodulin; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007632:Keratan Sulfate / Q000235:genetics; D015810:Linkage Disequilibrium; D000071234:Lumican; D008297:Male; D047728:Myopia, Degenerative / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011509:Proteoglycans / Q000235:genetics*; D012307:Risk Factors; D000071232:Small Leucine-Rich Proteoglycans
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; C119499:EPYC protein, human; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C490948:KERA protein, human; C000604306:LUM protein, human; D000071234:Lumican; D011509:Proteoglycans; D000071232:Small Leucine-Rich Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate