Association between genetic polymorphisms and axial length or related ocular biometric parameters

Purpose Myopia is a common eye disease, in which the cause and pathogenesis remain to be further elucidated. One of the notable changes closely linked to myopia is the elongation of axial length. Recent studies including genome-wide association studies have shown that genetic variants of candidate genes gap junction protein delta 2 (GJD2), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are associated with high myopia. The aim of the current study is to investigate the possible association between single nucleotide polymorphisms (SNPs) of the 3 candidate genes and eye axial length or other related ocular biometric parameters.
Methods A cohort of 459 middle-aged and elderly subjects with age ≥ 45 years old was recruited from Nan’ao Island in east Guangdong. The axial length, lens thickness and vitreous chamber depth in the subjects were measured by A-scan ultrasound biometry. The rs634990 near GJD2, rs6214 in IGF-1 and rs3735520 in HGF were genotyped using Taqman genotyping assay. The Hardy-Weinberg Equilibrium (HWE) was analyzed using Haploview version 4.2. The association between the parameters and the genotypes with different genetic models was accessed using multivariate linear regression implemented by the R statistical language, controlling age and sex.
Results All of the 3 SNPs showed high minor allele frequencies ranging from 42.7% to 49.0%. None of them deviated from HWE (all P-values > 0.05). The associations between the 3 SNPs and the axial length or vitreous depth were not statistically significant (all P-values > 0.05). However, the SNP rs6214 in IGF-1 was significantly associated with lens thickness in an additive model (P-value = 0.021). The regression coefficient of rs6214 was estimated to be 0.060±0.026 (coefficient±standard error). Analysis of dominant and recessive models for the SNP also showed similar results (P-values = 0.061 and 0.053 respectively). Association with lens thickness was not found in the other two SNPs.
Conclusions No evidence of association of GJD2 and IGF-1, HGF with the axial length was found in our cohort. However, the association between IGF-1 and lens thickness suggested that the myopia-associated gene IGF-1 might play a substantial role in the development of the eye ball, and probably in the etiology of high myopia. Further studies are thus warranted.