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Masahiro Miyake, Kenji Yamashiro, Hideo Nakanishi, Hisako Hayashi, Isao Nakata, Yumiko Akagi-Kurashige, Akitaka Tsujikawa, Kyoko Ohno-Matsui, Manabu Mochizuki, Nagahisa Yoshimura; Association of Paired Box 6 gene with High Myopia in Japanese. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6926.
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© ARVO (1962-2015); The Authors (2016-present)
The paired box 6 gene (PAX6) belongs to a highly conserved gene family of transcription factors and is involved in the development of the central nervous system and the eye. Especially in eye development, PAX6 is called as a master gene because it plays an important role during the lens and retina differentiation. PAX6 mutation causes macular hypoplasia, presenile cataract and congenital aniridia. Although the genetic association of PAX6 with high myopia has been shown in Caucasian, Taiwanese and Han Chinese, it has not been evaluated in Japanese. We conducted a case-control study in Japanese population.
A total of 1307 unrelated Japanese patients with high myopia (axial length≥26mm in both eyes) and two independent control groups were evaluated (333 cataract patients without high myopia and age-matched 923 healthy Japanese individuals). Mean age±SD was 57.1±15.0 years in high myopia group, 75.2±7.9 in cataract control, and 56.9±11.4 in healthy Japanese control. The age of the case group was not significantly different from the healthy Japanese control (P=0.85), while younger than the cataract control (P<0.0001). We genotyped 3 tag single-nucleotide polymorphisms (SNPs) in PAX6 - rs2071754, rs644242 and rs3026354. These 3 tag SNPs provided 100% coverage of all phase II Hapmap SNPs within PAX6 region (minor allele frequency≥0.10, r2 threshold of 0.90). The results were analyzed using multivariable logistic regression.
Genotype distributions in the 3 SNPs were in Hardy-Weinberg Equilibrium. After an adjustment of age and sex, evaluation with cataract control showed marginal association with high myopia in rs644242 (P=0.026), and significant association was observed when evaluated with healthy Japanese control (P=0.015). Because allele frequency did not differ in 2 control cohort, we pooled 2 control cohort to evaluate the association. This analysis revealed strong association of rs644242 with high myopia (P=0.004). The odds ratio (95% confidence interval) was 0.78 (0.65-0.92) for A allele. The other 2 SNPs did not show a significant association.
The current study showed a significant association of PAX6 with high myopia in Japanese. The allele A for rs644242 is a protective allele of high myopia.
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