1. Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk
- Author
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Kim, Sewon, Kim, Kyunglan, Heo, Dong Won, Kim, Jong-Sung, Park, Chan Kee, Kim, Chang-sik, and Kang, Changwon
- Subjects
Adult ,Male ,genetic structures ,Caveolin 2 ,Caveolin 1 ,Glaucoma ,Middle Aged ,Polymorphism, Single Nucleotide ,eye diseases ,Asian People ,Gene Frequency ,Risk Factors ,Case-Control Studies ,Republic of Korea ,Humans ,Female ,Genetic Predisposition to Disease ,RNA, Messenger ,Genetic Association Studies ,Glaucoma, Open-Angle ,Intraocular Pressure ,Research Article ,Aged - Abstract
Purpose 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.
- Published
- 2015