Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia

[摘要] Purpose: Numerous studies, includingthose using animal models of myopia development and human clinicaltrials, have shown that the non-selective muscarinic antagonistatropine is effective in preventing the axial elongation that leads tomyopia development. Among all of the muscarinic acetylcholine receptors(mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eyechange. Our specific aim in this study was to examine the associationbetween high myopia and polymorphisms within the muscarinicacetylcholine receptors 1 gene (CHRM1). Methods: The participants comprised of ahigh myopia group (n=194; age range, 17–24 years) having a myopicspherical equivalent greater than 6.5 diopters (D) and a control group(n=109; age range, 17–25 years) having a myopic spherical equivalentless than 0.5 D. Genotyping was performed using an assay-on-demandallelic discrimination assay. Polymerase chain reaction (PCR) wasperformed using 96 well plates on a thermal cycler. The polymorphismsdetected were S1 (CHRM1rs11823728),S2 (CHRM1rs544978),S3 (CHRM1rs2186410),and S4 (CHRM1rs542269).Results: There was a significantdifference in the distribution of S2 and S4 between the high myopia andcontrol groups (p=2.40×10−6 and 2.38×10-8,respectively). The odds ratios of AA genotype of S2 and GG genotype ofS4 were both 0.08 (95% confidence interval [CI]: 0.02–0.29 and0.02–0.36, respectively). Logistic regression test revealed S1, S2, andS4 CHRM1 as all being significant in the development of highmyopia. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A)differed significantly between the two groups (p=3.4×10−5,odds ratio: 0.1, 95% CI: 0.03–0.34). Conclusions: Our results suggest thatthe S2 and S4 polymorphisms of CHRM1 are associated withsusceptibility for developing high myopia. S1, S2, and S4 CHRM1had a co-operative association with high myopia.

[学科分类] 生物化学/生物物理