title: Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk.
abstract: OBJECTIVE
  The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma.
  
  
  METHODS
  Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data.
  
  
  RESULTS
  Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis.
  
  
  CONCLUSIONS
  The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Sewon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Kyunglan
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Heo
authors.affiliation: Department of Family Medicine, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Jong-Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea.
authors.forename: Chan Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Chang-sik
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Changwon
authors.initials: C
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics*; D051243:Caveolin 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005901:Glaucoma / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056910:Republic of Korea; D012307:Risk Factors
chemical_list: C495540:CAV1 protein, human; C495544:CAV2 protein, human; D051242:Caveolin 1; D051243:Caveolin 2; D012333:RNA, Messenger