Introduction. Even though ocular refractive state is highly heritable and under strong genetic control, the identification of\nsusceptibility genes remains a challenge. Several HGF (hepatocyte growth factor) gene variants have been associated with\nocular refractive errors and corneal pathology. Purpose. Here, we assess the association of an HGF gene variant, previously\nreported as associated with hyperopia, and ocular biometric parameters in a multicenter Spanish cohort. Methods. An\nobservational prospective multicenter cross-sectional study was designed, including a total of 403 unrelated subjects\ncomprising 188 hyperopic children (5 to 17 years) and 2 control groups: 52 emmetropic adolescents (13 to 17 years) and 163\nemmetropic young adults (18 to 28 years). Each individual underwent a comprehensive eye examination including cycloplegic\nrefraction, and topographic and ocular biometric analysis. Genomic DNA was extracted from oral swabs. HGF single\nnucleotide polymorphism (SNP) rs12536657 was genotyped. Genotypic, allelic, and logistic regression analyses were performed\ncomparing the different groups. A quantitative trait association test analyzing several biometric parameters was also\nperformed using generalized estimating equations (GEEs) adjusting for age and gender. Results. No association between\nrs12536657 and hyperopia was found through gender-adjusted logistic regression comparing the hyperopic children with\neither of the two control groups. Significant associations between mean topographic corneal curvature and rs12536657 for G/\nA (slope =+0.32; CI 95%: 0.04-0.60;p =0.023) and A/A (slope = +0.76; CI 95%: 0.12-1.40; p = 0.020) genotypes were\nobserved with the age- and gender-adjusted univariate GEE model. Both flat and steep corneal topographic meridians were\nalso significantly associated with rs12536657 for the G/A and A/A genotypes. No association was found between rs12536657\nand any other topographic or biometric measurements. Conclusions. Our results support a possible role for HGF gene variant\nrs12536657 in corneal curvature in our population. To our knowledge, this is the first multicenter quantitative trait association\nstudy of HGF genotypes and ocular biometric parameters comprising a pediatric cohort.
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