title: Multiple gene polymorphisms analysis revealed a different profile of genetic polymorphisms of primary open-angle glaucoma in northern Chinese.
abstract: OBJECTIVE
  To evaluate the individual and interactive effects of polymorphisms in the myocilin (MYOC),optineurin (OPTN), WD repeat domain 36 (WDR36), and apolipoprotein E (APOE) genes on primary open-angle glaucoma (POAG) in northern Chinese.
  
  
  METHODS
  Northern Chinese study subjects, 176 POAG patients and 200 controls, were recruited for screening of the coding exons and splicing regions of MYOC. Five single nucleotide polymorphisms (SNPs) in OPTN (M98K, R545Q, IVS5+38T>G, IVS8-53T>C, and IVS15+10G>A), one SNP in WDR36 (IVS5+30C>T) as well as the APOE promoter and epsilon2/epsilon3/epsilon4 polymorphisms were also examined. Association analysis was performed by using chi(2) analysis. High-order gene-gene interaction was also analyzed using the multifactor dimensionality reduction (MDR) method.
  
  
  RESULTS
  In MYOC, 22 variants were identified. Four of them were novel but found in controls only. The missense mutation, Val53Ala, is likely a glaucoma causing mutation, accounting for 0.6% of cases. No individual polymorphism in OPTN, WDR36, or APOE was associated with POAG. MDR analysis identified a best 6-factor model for POAG: MYOC IVS2+35A>G, OPTN Met98Lys, OPTN IVS5+38T>G, OPTN IVS8-53T>C, WDR36 IVS5+30C>T, and APOE -491A>T.
  
  
  CONCLUSIONS
  The association pattern between the genes, MYOC, OPTN, WDR36, and APOE, and POAG in northern Chinese is different from that of southern Chinese. Disease-causing mutations in MYOC accounted for a small proportion of northern Chinese POAG patients. Common polymorphisms in these genes were not associated with POAG individually but might interactively contribute to the disorder, supporting a polygenic etiology.
authors.affiliation: Beijing Tongren Hospital of the Capital Medical University, Beijing, China.
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Jia
authors.forename: Pancy Oi-Sin
authors.initials: PO
authors.lastname: Tam
authors.forename: Sylvia Wai-Yee
authors.initials: SW
authors.lastname: Chiang
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.forename: Li Jia
authors.initials: LJ
authors.lastname: Chen
authors.forename: Gary Hin-Fai
authors.initials: GH
authors.lastname: Yam
authors.forename: Chi-Pui
authors.initials: CP
authors.lastname: Pang
authors.forename: Ning-Li
authors.initials: NL
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D002681:China; D003598:Cytoskeletal Proteins / Q000235:genetics; D004843:Epistasis, Genetic; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D035582:Transcription Factor TFIIIA / Q000235:genetics; D000099179:Myocilin
chemical_list: D001057:Apolipoproteins E; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human; C502341:WDR36 protein, human