Article section: Clinical/Epidemiologic Research

PURPOSE. This study examined the relationship between high myopia and three myopia candidate genes, namely matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 and 3 (TIMP2 and TIMP3), involved in scleral remodeling. METHODS. The study recruited unrelated adult Han Chinese who were high myopes (spherical equivalent ≤-6.0D for both eyes; cases) and emmetropes (within ±1.0D for both eyes; controls). Sample Set 1 had 300 cases and 300 controls while Sample Set 2 had 356 cases and 354 controls. Forty-nine tag single nucleotide polymorphisms (SNPs) were selected from these candidate genes. The first stage was an initial screen of 6 case pools and 6 control pools constructed from Sample Set 1, each pool consisting of 50 distinct subjects of the same affection status. In the second stage, " positive " SNPs from the first stage were confirmed by genotyping individual samples forming the DNA pools. In the third stage, positive SNPs from stage 2 were replicated with Sample Set 2 genotyped individually. (nested ANOVA) and were followed up by individual genotyping. Of the 3 SNPs genotyped, two TIMP3 SNPs were found significantly associated with high myopia by single-marker or haplotype analysis. However, the initial positive results could not be replicated by Sample Set 2. CONCLUSIONS. MMP2, TIPM2 and TIMP3 genes were not associated with high myopia in Chinese and hence were unlikely to play a major role in the genetic susceptibility to high myopia.