Ethnicity-Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta-Analysis

Ann Hum Genet. 2015 Nov;79(6):431-50. doi: 10.1111/ahg.12128. Epub 2015 Sep 24.

Abstract

Pseudoexfoliation (PEX) is an age-related disorder of the extracellular matrix; it is strongly associated with glaucoma, the leading cause of irreversible blindness worldwide. We conducted an ethnic-based meta-analysis of the association of LOXL1 polymorphisms with PEX/pseudoexfoliative glaucoma (PEXG). Association studies were retrieved systematically from PubMed, EMBASE, and Web of Knowledge. Allelic and genotype frequencies of rs3825942, rs1048661, and rs2165241 were compared between PEX/PEXG and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Overall, 39 independent cohorts were included. Rs3825942 (G) was an at risk allele for PEX/PEXG in Caucasians, Japanese, Koreans, Chinese, South Asians, and Middle Easterners, but protective in Black South Africans (OR = 0.10, 95%CI:0.06-0.16). Rs1048661 (G) was an at risk allele for PEX/PEXG in Caucasians, South Asians, Middle Easterners and Black South Africans, but was protective in Japanese (OR = 0.03, 95%CI:0.02-0.06) and Koreans (OR = 0.10, 95%CI:0.05-0.22). These associations we-re confirmed for the genotypic recessive models. Rs2165241 (C) was a protective allele for PEX/PEXG in Caucasians, but was an at risk allele in Japanese (OR = 7.49, 95%CI:3.22-17.41) and Koreans (OR = 6.63, 95%CI:2.60-16.90). This was confirmed for the genotypic dominant model. Other genetic and/or environmental factors may modify the effect of LOXL1 polymorphisms in certain ethnic groups.

Keywords: LOXL1; Pseudoexfoliation syndrome; exfoliation; genetic polymorphisms; glaucoma; pseudoexfoliative glaucoma.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Oxidoreductases / genetics*
  • Asian People / genetics
  • Black People / genetics
  • Confidence Intervals
  • Ethnicity / genetics
  • Exfoliation Syndrome / ethnology*
  • Exfoliation Syndrome / genetics*
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Humans
  • Models, Statistical
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • White People / genetics

Substances

  • Amino Acid Oxidoreductases
  • LOXL1 protein, human