Assessment of the association of matrix metalloproteinases with myopia, refractive error and ocular biometric measures in an Australian cohort.

Extracellular matrix proteins have been implicated in protein remodelling of the sclera in refractive error. The matrix metalloproteinases (MMPs) falling into the collagenase (MMP1, MMP8, MMP13), gelatinase (MMP2, MMP9) and stromelysin (MMP3, MMP10, MMP11) functional groups are particularly important. We wished to assess their association with myopia, refractive error and ocular biometric measures in an Australian cohort. A total of 543 unrelated individuals of Caucasian ethnicity were genotyped including 269 myopes (≤-1.0D) and 274 controls (>-1.0D). Tag single nucleotide polymorphisms (SNPs) (n = 53) were chosen to encompass these eight MMPs. Association tests were performed using linear and logistic regression analysis with age and gender as covariates. Spherical equivalent, myopia, axial length, anterior chamber depth and corneal curvature were the phenotypes of interest. Initial findings indicated that the best p values for each trait were 0.02 for myopia at rs2274755 (MMP9), 0.02 for SE at both rs3740938 (MMP8) and rs131451 (MMP11), 0.01 for axial length at rs11225395 (MMP8), 0.01 for anterior chamber depth at rs498186 (MMP1) and 0.02 at rs10488 (MMP1). However, following correction for multiple testing, none of these SNPs remained statistically significant. Our data suggests that the MMPs in the collagenase, gelatinase and stromelysin categories do not appear to be associated with myopia, refractive error or ocular biometric measures in this cohort.

Assessment of TGIF as a candidate gene for myopia.

PURPOSE: Transforming growth beta-induced factor (TGIF) has been identified as a candidate gene for high myopia through genetic linkage studies and through its role in ocular growth in animal studies. However, the association of single nucleotide polymorphisms (SNPs), based solely on myopia refraction, has so far been inconclusive. This is the first study conducted to investigate the association of TGIF with refraction and ocular biometric measurements. METHODS: Twelve tag SNPs (tSNPs) encompassing the TGIF gene and 2 kb upstream of its promoter region were used to evaluate the association between TGIF variants with both ocular biometric measures and refraction. A total of 257 cases of myopia (spherical equivalent [SE] worse than -0.50 D) and 294 control subjects (no myopia) were genotyped. Genotype frequencies were analyzed by chi(2) test and one-way ANOVA. RESULTS: Two tSNPs showed significant association with biometric measures, with the SNP rs8082866 being associated with both axial length (P = 0.013) and corneal curvature (P = 0.007) and the SNP rs2020436 being associated with corneal curvature (P = 0.022). However, these associations became nonsignificant after multiple testing (Bonferroni correction). CONCLUSIONS: Findings of this study suggest that the TGIF gene is unlikely to play a major role in either ocular biometric measures or refraction in a Caucasian population. Future studies should focus on other genes in the MYP2 linkage region or other linked regions to identify myopia-causing genes.