Objective: To investigate the genetic association between transforming growth factor beta1 (TGFB1) gene polymorphisms and high myopia in a Chinese population.
Methods: Six hundred adults were recruited for this case-control study, including 300 subjects with high myopia (-8.0 diopters or worse) and 300 control subjects (within +/-1.0 diopters). Seven tag single-nucleotide polymorphisms (SNPs) and 1 coding SNP were genotyped. Their frequencies were compared between cases and controls by statistical tests.
Results: Four SNPs in the 5' half of the gene showed significant differences in allele and genotype frequencies between cases and controls. The results remained significant after correction for multiple comparisons. The previously reported association of the coding SNP rs1800470 with high myopia was successfully replicated. The tag SNP rs4803455 in intron 2 was found to account for the positive results of the other 3 SNPs by stepwise logistic regression. The minor allele T of rs4803455 was protective against high myopia with an odds ratio of 0.67 (95% confidence interval, 0.53-0.86; P= .001).
Conclusion: TGFB1 is a myopia susceptibility gene.
Clinical relevance: TGFB1 is the first myopia susceptibility gene successfully replicated. The functional significance of rs4803455 or the genuine causative SNPs in linkage disequilibrium with it remains to be determined.