title: A DNA pooling-based case-control study of myopia candidate genes COL11A1, COL18A1, FBN1, and PLOD1 in a Chinese population.
abstract: OBJECTIVE
  We examined the relationship between high myopia and common polymorphisms in four candidate genes: collagen, type XI, alpha 1 (COL11A1); collagen, type XVIII, alpha 1 (COL18A1); fibrillin 1 (FBN1); and procollagen-lysine 1,2-oxoglutarate 5-dioxygenase 1 (PLOD1). These genes were selected because rare pathogenic mutations in these genes cause disease syndromes that have myopia, usually high myopia, as one of the common presenting features.
  
  
  METHODS
  This study recruited 600 unrelated Han Chinese subjects including 300 cases with high myopia (spherical equivalent or SE≤-8.00 diopters) and 300 controls (SE within ±1.00 diopter). A total of 66 tag single nucleotide polymorphisms (SNPs) were selected for study from these four candidate genes. The study adopted a DNA pooling strategy with an initial screen of DNA pools to identify putatively positive SNPs and then confirmed the "positive" SNPs by genotyping individual samples forming the original DNA pools. DNA pools were each constructed by mixing equal amounts of DNA from 50 individuals with the same phenotype status. Six case pools were prepared from 300 cases and six control pools from 300 controls. Allele frequencies of DNA pools were estimated by analyzing the primer-extended products with denaturing high performance liquid chromatography and compared between case pools and control pools with nested ANOVA.
  
  
  RESULTS
  In the first stage, 60 SNPs from the 4 candidate genes were successfully screened using the DNA pooling approach. Of these, 6 SNPs showed a statistical significant difference in estimated allele frequencies between case pools and controls at p<0.10. In the second stage, these "positive" SNPs were followed up by individual genotyping, but failed to be confirmed via standard single-marker and haplotype analyses.
  
  
  CONCLUSIONS
  Common polymorphisms in these four candidate genes (COL11A1, COL18A1, FBN1 and PLOD1) were unlikely to play important roles in the genetic susceptibility to high myopia.
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China. shea.ping.yip@inet.polyu.edu.hk
authors.forename: Shea Ping
authors.initials: SP
authors.lastname: Yip
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Leung
authors.forename: Wai Yan
authors.initials: WY
authors.lastname: Fung
authors.forename: Po Wah
authors.initials: PW
authors.lastname: Ng
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Maurice K H
authors.initials: MK
authors.lastname: Yap
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D024161:Collagen Type XI / Q000235:genetics* / Q000378:metabolism; D043170:Collagen Type XVIII / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000032:analysis; D016172:DNA Fingerprinting; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009216:Myopia / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D054392:Adipokines
chemical_list: D024161:Collagen Type XI; D043170:Collagen Type XVIII; D004247:DNA; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; C000605722:FBN1 protein, human; D054392:Adipokines