The association of single nucleotide polymorphism and haplotype at the decorin, lumican, and dermatan sulfate proteoglycan 3 (DSPG3) genes with susceptibility to high myopia
Date Issued
2008
Date
2008
Author(s)
Chen, Zoe Tzu-Yi
Abstract
Scleral thinning and eyeball elongation in myopic eyes are related to the remodeling of scleral extracellular matrices. Small Leucine-Rich Proteoglycans (SLRPs) in human sclera play an important role in regulating the assembly and interaction of collagen fibrils, which influence scleral mechanical properties and axial elongation. Mutations in SLRP genes have been reported in common high myopia. Chromosome 12q21-23 (MYP 3), linked with certain familial high myopia, includes three SLRP genes, which are decorin, lumican, and dermatan sulfate proteoglycan 3 (DSPG-3). y 120 cases and 137 controls, we evaluated the association of SNPs and haplotypes at the decorin, lumican, and DSPG3 genes with high myopia susceptibility in Taiwanese patients. We genotyped 4, 8, and 4 SNPs, respectively, within these three genes by using direct DNA sequencing. The lumican gene SNP rs3759223: T>C showed significant associations with high myopia (p=2.83×10-4). 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 ×10-6). Haplotype-specific tests showed that the C-C and T-C haplotypes were significantly associated with high myopia, with odds ratios (95% confidence interval) of 19.32 (2.55-146.54) and 0.69(0.46-1.04), respectively. In high myopia cases, those with C-C haplotype tend to have more severe myopia and longer axial length. rs3759223 and rs3741834 are in putative regulatory element of lumican gene which influences fibrillogenesis of scleral collagen fibers and the myopia development. The results of a multifactor dimensionality reduction (MDR) analysis corroborated the single-locus association and suggested a significant two-locus interaction model composed of SNPs rs2300588 and rs3741834 in the lumican gene. enetic variation in regulatory domains of the lumican gene, where both rs3759223 and rs3741834 locate, in Han Chinese may be associated with high myopia susceptibility, making this region worthy of further investigation！
Subjects
high myopia
single nucleotide polymorphism
haplotype
lumican
association
case-control study
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