Association of the <i>ZC3H11B, ZFHX1B</i> and <i>SNTB1</i> genes with myopia of different severities.

Abstract

To investigate the associations of single-nucleotide polymorphisms (SNPs) in the <i>ZC3H11B, ZFHX1B, VIPR2</i>, <i>SNTB1</i> and <i>MIPEP</i> genes with severities of myopia in Chinese populations. Based on previous myopia genome-wide association studies, five SNPs (<i>ZC3H11B</i> rs4373767, <i>ZFHX1B</i> rs13382811, <i>VIPR2</i> rs2730260, <i>SNTB1</i> rs7839488 and <i>MIPEP</i> rs9318086) were selected for genotyping in a Chinese cohort of 2079 subjects: 252 extreme myopia, 277 high myopia, 393 moderate myopia, 366 mild myopia and 791 non-myopic controls. Genotyping was performed by TaqMan assays. Allelic frequencies of the SNPs were compared with myopia severities and ophthalmic biometric measurements. The risk allele T of <i>ZC3H11B</i> SNP rs4373767 was significantly associated with high myopia (OR=1.39, p=0.007) and extreme myopia (OR=1.34, p=0.013) when compared with controls, whereas <i>ZFHX1B</i> rs13382811 (allele T, OR=1.33, p=0.018) and <i>SNTB1</i> rs7839488 (allele G, OR=1.71, p=8.44E-05) were significantly associated with extreme myopia only. In contrast, there was no significant association of these SNPs with moderate or mild myopia. When compared with mild myopia, subjects carrying T allele of rs4373767 had a risk of progressing to high myopia (spherical equivalent ≤-6 dioptres) (OR=1.29, p=0.017). Similarly, the T allele of rs13382811 also imposed a significant risk to high myopia (OR=1.36, p=0.007). In quantitative traits analysis, SNPs rs4373767, rs13382811 and rs7839488 were correlated with axial length and refractive errors. We confirmed <i>ZC3H11B</i> as a susceptibility gene for high and extreme myopia, and <i>ZFHX1B</i> and <i>SNTB</i> for extreme myopia in Chinese populations. Instead of myopia onset, these three genes were more likely to impose risks of progressing to high and extreme myopia.