Objective: To investigate the association of genetic polymorphisms in the dermatan sulfate proteoglycan 3 (DSPG3), lumican (LUM), and decorin (DCN) genes (component genes of the sclera) with high myopia susceptibility in Taiwanese people.
Design: Prospective case-control study.
Participants: Hospital clinic-based samples of 120 unrelated patients with extremely high myopia were studied. One hundred thirty-seven unrelated emmetropic individuals served as controls.
Methods: Four, 8, and 4 single nucleotide polymorphism (SNPs) were genotyped within the DSPG3, lumican, and decorin genes, respectively, using direct DNA sequencing. Pairwise linkage disequilibrium, haplotype analysis, adjusted logistic regression, and multifactor dimensionality reduction (MDR) methods were used to determine significant associations.
Main outcome measures: The association of haplotypes at the lumican gene with high myopia development.
Results: The lumican gene SNP rs3759223:T-->C demonstrated a significant association with high myopia (P = 2.83 x 10(-4)). Four lumican SNPs showed significant linkage disequilibrium and formed a haplotype block. Sliding window haplotype analyses revealed that the block consisting of rs3759223 and rs3741834 showed significant goodness of fit (global P = 1.0725 x 10(-6)). Haplotype-specific tests showed that the C-C and T-C haplotypes were associated significantly with high myopia, with odds ratios (95% confidence intervals) of 19.32 (2.55-146.54) and 0.69 (0.46-1.04), respectively. rs3759223 and rs3741834 are in a putative regulatory element of the lumican gene, which influences fibrillogenesis of scleral collagen fibers and the development of myopia. The results of an MDR analysis corroborated the single-locus association and suggested a significant 2-locus interaction model composed of SNPs rs2300588 and rs3741834 in the lumican gene.
Conclusions: Genetic variation in the regulatory domains of the lumican gene, where both rs3759223 and rs3741834 are located, are associated with high myopia susceptibility among the Han Chinese, making this region worthy of further investigation.