Genetic association between corneal curvature-related genes and high myopia in Chinese Han population

Background

High myopia is one of the primary factors of visual impairment, and its prevention and management are researching hot topics.Corneal curvature (CC) measures the steepness of the cornea which is an important parameter leading to myopia.Genome-wide association study (GWAS) showed that several genes are associated with CC in Asian populations.However, the association of corneal curvature-related genes with high myopia is unclear up to now.

Objective

This study was to investigate the association between single nucleotide polymorphism (SNP) in the rs74225573 (mechanistic target of rapamycin [MTOR]), rs60078183 (cytidine/uridine monophosphate kinase 1[CMPK1]), rs1800813 (platelet derived growth factor receptor alpha[PDGFRA]), rs11204213 (retinol binding protein 3[RBP3]) and high myopia in Chinese Han population.

Methods

A prospective cohort study was performed.Four hundreds and eighty-three patients with high myopia were collected in Sichuan Provincial People’s Hospital from February 2012 to August 2013, with the diopter (-10.84±4.69)D in the right eyes and (-10.35±4.67)D in the left eyes or ocular axial length of (28.15±2.27)mm in the right eyes and (27.72±2.51)mm in the left eyes.Five hundreds and nineteen normal volunteers matched in age and gender were included in the same period as controls, and all the subjects were Chinese Han people without genetic relationship.The periphery blood of 4 ml was obtained for the DNA extraction from each subject under the written informed consent.The primers of rs74225573, rs60078183, rs1800813 and rs11204213 were designed based on the information of NCBI website.The four SNPs were amplified by real-time PCR and genotyped by SNaPshot method.

Results

All the genotype frequencies of these four SNPs were in Hardy-Weinberg equilibrium (HWE). There are no significant differences in minor allele frequency (MAF) distribution of rs74225573, rs60078183 and rs11204213 between high myopia group and normal control group (rs74225573: P_{age–corrected} =0.935, OR=0.98; rs60078183: P_{age–corrected} =0.782, OR=1.04; rs11204213: P_{age–corrected}=0.058, OR=1.66), and the MAF of rs1800813 was significantly higher in the high myopia group than that in the normal control group (P_{age–corrected}=0.001, OR=0.64). The genotype frequency of rs74225573, rs60078183 and rs11204213 was not evidently different in additive model 1(AB vs.BB), additive model 2 (AA vs.BB), dominant model (AA+ AB vs.BB) and recessive model (AA vs.AB+ BB) (all at P>0.05), while significant differences were found in genotype frequency of rs1800813 both in additive model 1 and dominant model (additive model 1: P=0.002, OR=0.59; dominant model: P=0.001, OR=0.58).

Conclusions

The SNP of rs1800813 in the PDGFRA gene is associated with the pathogenesis of high myopia in the Chinese Han population, but the SNPs of rs74225573 (MTOR gene), rs60078183 (CMPK1 gene) and rs11204213 (RBP3 gene) appear to be not associated with high myopia.