Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia

Numerous studies, including those using animal models of myopia development and human clinical trials, have shown that the non-selective muscarinic antagonist atropine is effective in preventing the axial elongation that leads to myopia development. Among all of the muscarinic acetylcholine receptors (mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eye change. Our specific aim in this study was to examine the association between high myopia and polymorphisms within the muscarinic acetylcholine receptors 1 gene (CHRM1).

The participants comprised of a high myopia group (n=194; age range, 17-24 years) having a myopic spherical equivalent greater than 6.5 diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on-demand allelic discrimination assay. Polymerase chain reaction (PCR) was performed using 96 well plates on a thermal cycler. The polymorphisms detected were S1 (CHRM1rs11823728), S2 (CHRM1rs544978), S3 (CHRM1rs2186410), and S4 (CHRM1rs542269).

There was a significant difference in the distribution of S2 and S4 between the high myopia and control groups (p=2.40 x 10(-6) and 2.38 x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36, respectively). Logistic regression test revealed S1, S2, and S4 CHRM1 as all being significant in the development of high myopia. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34).

Our results suggest that the S2 and S4 polymorphisms of CHRM1 are associated with susceptibility for developing high myopia. S1, S2, and S4 CHRM1 had a co-operative association with high myopia.