Assessment of TGIF as a Candidate Gene for Myopia

Centre for Eye Research Australia, Department of Ophthalmology University of Melbourne, 32 Gisborne Street, East Melbourne, Victoria, Australia.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.4). 02/2008; 49(1):49-54. DOI: 10.1167/iovs.07-0896
Source: PubMed


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.
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.
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).
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.

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    • "Australian twins from the GEM study have also been incorporated into studies investigating candidate genes for myopia and refractive errors. Twins from the GEM study were used as part of a larger cohort that assessed genetic associations between the genes transforming growth betainduced factor (TGIF), retinoic acid receptor alpha (RARA), hepatocyte growth factor receptor (cMET), and hepatocyte growth factor (HGF) and the traits of myopia, ocular refraction , ocular axial length, corneal curvature, and anterior chamber depth (Pertile et al., 2008; Schache et al., 2009; Veerappan et al., 2009a, 2009b). These studies showed that the TGIF, RARA, and cMET genes are not likely to be associated with these ophthalmic traits. "
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    • "Therefore, no association was found at this level for multiple comparisons in the high myopia group. The Bonferroni correction is commonly applied in association studies to evaluate the significance of multiple testing of SNPs, but it is usually too conservative [16]. We realize that this correction is a limitation and it may lead to loss of significant findings. "
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