Association of paired box 6 with high myopia in Japanese

Abstract

Purpose: The objective of this study was to investigate whether genetic variations in the paired box 6 (PAX6) gene are associated with high myopia in Japanese subjects.

Methods: A total of 1,307 unrelated Japanese patients with high myopia (axial length ≥26 mm in both eyes) and two independent control groups were evaluated (333 cataract patients without high myopia and 923 age-matched healthy Japanese individuals). We genotyped three tag single-nucleotide polymorphisms (SNPs) in PAX6: rs2071754, rs644242, and rs3026354. These SNPs provided 100% coverage of all phase II HapMap SNPs within the PAX6 region (minor allele frequency ≥0.10; r(2) threshold: 0.90). Chi-square tests for trend and multivariable logistic regression were conducted.

Results: Genotype distributions in the three SNPs were in accordance with the Hardy-Weinberg equilibrium. After adjusting for age and sex, evaluation of cataract control showed a marginal association with high myopia in rs644242 (odds ratio [95% confidence interval]=0.69 [0.49-0.96], p=0.026), and a significant association was observed in healthy Japanese controls (0.79 [0.66-0.96], p=0.015). We pooled two control cohorts to evaluate the association. This analysis revealed a strong association between rs644242 and high myopia (0.78 [0.65-0.92], p=0.0045). The rs644242 A allele was a protective allele for development of high myopia. Subanalysis also revealed that rs644242 was significantly associated with extreme high myopia (0.78 [0.64-0.95], p=0.0165). The other two SNPs did not show a significant association with this condition.

Conclusions: The current study showed a significant association of PAX6 with high and extreme myopia in Japanese participants. The A allele of rs644242 is a protective allele.

Figure 1

Collaborative effect of CTNND2 rs6885224 and PAX6 rs644242 on high myopia. The odds ratio of each genotype-pairs was calculated adjusting for age and sex. Patients with both the rs644242 AA genotype (non-risk homo) and the rs6885224 TT genotype (non-risk homo) are set as the reference (odds ratio=1.0). The number of subjects with rs6885224 CC and rs644242 CC were 55 in the case group and 42 in the control group, 286 in the case group and 252 in the control group with rs6885224 CT and rs644242 CC, 392 in the case group and 416 in the control group with rs6885224 TT and rs644242 CC, 15 in the case group and nine in the control group with rs6885224 CC and rs644242 CA, 70 in the case group and 78 in the control group with rs6885224 CT and rs644242 CA, 76 in the case group and 108 in the control group with rs6885224 TT and rs644242 CA, three in the case group and nine in the control group with rs6885224 CT and rs644242 AA, and six in the case group and nine in the control group with rs6885224 TT and rs644242 AA.