Endophenotyping reveals differential phenotype-genotype correlations between myopia-associated polymorphisms and eye biometric parameters

Mol Vis. 2012:18:765-78. Epub 2012 Mar 30.

Abstract

Purpose: To investigate the association with ocular biometric parameters in myopia-associated single nucleotide polymorphisms (SNPs) of the gap junction protein delta 2 (GJD2), insulin-like growth factor-1 (IGF1) and hepatocyte growth factor (HGF) genes in two geographically different Chinese cohorts.

Methods: In 814 unrelated Han Chinese individuals aged above 50 years including 362 inland residents and 432 island dwellers, comprehensive ophthalmic examinations were performed. Three SNPs, including GJD2 rs634990, IGF1 rs6214, and HGF rs3735520, were genotyped. Genetic association with ocular biometric parameters was analyzed in individual cohorts, using linear regression controlled for sex and age. Common associations shared by the two cohorts were revealed by meta-analysis.

Results: Meta-analysis showed that GJD2 rs634990 alone was not associated with any biometric parameters (adjusted p>0.645). The T allele of IGF1 rs6214 was specifically associated with thicker lens (β±SE=0.055±0.022, adjusted p=0.034). The A allele of HGF rs3735520 was associated with longer vitreous chamber depth (β±SE=0.143±0.060, adjusted p=0.050). Significant interaction between HGF rs3735520 and GJD2 rs634990 was found in association with axial length and vitreous chamber depth (adjusted p=0.003 and 0.033, respectively), and possibly with spherical error (adjusted p=0.056).

Conclusions: Our endophenotyping analysis showed differential association between selected myopia-associated genes and ocular biometric parameters in our Chinese cohorts, which may underline substantial but diversified effects of these genes and their interaction on the development of eye structure and etiology of myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People / genetics*
  • Biometry
  • China
  • Connexins / genetics*
  • Eye / metabolism*
  • Eye / pathology
  • Female
  • Gap Junction delta-2 Protein
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Geography
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Myopia / genetics*
  • Myopia / pathology
  • Phenotype
  • Polymorphism, Single Nucleotide

Substances

  • Connexins
  • HGF protein, human
  • Hepatocyte Growth Factor
  • Insulin-Like Growth Factor I