SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma.

Abstract

PURPOSE:

To investigate the associations between gene variants in cholesterol 24S-hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG).

METHODS:

We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts.

RESULTS:

Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, p(rec)=0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG (p(dom)=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028).

CONCLUSIONS:

Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association.

• Authors: Li Jia Chen, Pancy O S Tam, Dexter Y L Leung, Alex H Fan, Mingzhi Zhang, Clement C Y Tham, Sylvia W Y Chiang, Bao Jian Fan, Ningli Wang, Chi Pui Pang
• Journal: Molecular vision (Mol Vis) Vol. 18 Pg. 1629-39 ( 2012) ISSN: 1090-0535 [Electronic] United States
• PMID: 22773901 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• TLR4 protein, human
• Toll-Like Receptor 4

Topics

• Adolescent
• Adult
• Age Factors
• Age of Onset
• Aged
• Aged, 80 and over
• Asian People (genetics)
• Child
• Chromosomes, Human, Pair 2 (genetics)
• Cohort Studies
• Female
• Genes, Recessive
• Genetic Association Studies
• Genetic Loci (genetics)
• Genetic Predisposition to Disease
• Glaucoma, Open-Angle (genetics)
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• Toll-Like Receptor 4 (genetics)