Association of PDGFRA polymorphisms with the risk of corneal astigmatism in a Japanese population

Abstract

Corneal astigmatism is reportedly associated with polymorphisms of the platelet-derived growth factor receptor alpha (PDGFRA) gene region in Asian populations of Chinese, Malay, and Indian ancestry and populations of European ancestry. In this study, we investigated whether these PDGFRA polymorphisms are associated with corneal astigmatism in a Japanese population. We recruited 1,535 cases with corneal astigmatism (mean corneal cylinder power across both eyes: ≤ - 0.75 diopters [D]) and 842 controls (> - 0.75 D) to genotype 13 single-nucleotide polymorphisms (SNPs) in the PDGFRA gene region. We also performed imputation analysis in the region, with 179 imputed SNPs included in the statistical analyses. The PDGFRA SNPs were not significantly associated with the cases with corneal astigmatism ≤ - 0.75 D. However, the odds ratios (ORs) of the minor alleles of SNPs in the upstream region of PDGFRA, including rs7673984, rs4864857, and rs11133315, tended to increase according to the degree of corneal astigmatism, and these SNPs were significantly associated with the cases with corneal astigmatism ≤ - 1.25 D or ≤ - 1.50 D (Pc < 0.05, OR = 1.34-1.39). These results suggest that PDGFRA SNPs play a potential role in the development of greater corneal astigmatism.

Figure 1

In-depth SNP analysis of the PDGFRA gene region in the Japanese cohort. Data are shown for the cases with corneal astigmatism (a) ≤  − 1.25 D or (b) ≤  − 1.50 D. (Top row) Posterior inclusion probability for each SNP genotyped and imputed in the current study. (Middle row) Regional association plot for each SNP. The left y-axes represent the − log10 P values for associations with corneal astigmatism; the right y-axes represent the estimated recombination rate. The horizontal blue and red lines indicate P = 0.05 and Pc = 0.05 (i.e. P = 0.05/9), respectively. One of the lead SNPs in each of the cases with corneal astigmatism ≤  − 1.25 D and ≤  − 1.50 D, (a) rs7673984 and (b) rs11133315, respectively, is depicted as a purple diamond. The color coding for all other SNPs indicates linkage disequilibrium with (a) rs7673984 or (b) rs11133315 as follows: red, r² ≥ 0.8; yellow, 0.6 ≤ r² < 0.8; green, 0.4 ≤ r² < 0.6; cyan, 0.2 ≤ r² < 0.4; and blue, r² < 0.2. (Bottom row) Gene annotations.