Association between <i>CHRM1</i> gene polymorphisms and genetic susceptibility to high myopia in the Han population of Henan province_Chinese Journal of Ocular Fundus Diseases

Authors：

Yang Fan , Zhang Min , An Guangqi , Gao Wenna , Du Liping ,  Jin Xuemin

Department of ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;

Corresponding author：

Jin Xuemin, Email: 2740913223@qq.com

Keywords：

High myopia; CHRM1 gene; Han population in Henan Province; Single nucleotide polymorphism

DOI：

10.3760/cma.j.cn511434-20240909-00348

Video：

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Objective To investigate the relationship between single nucleotide polymorphisms (SNP) in the CHRM1 gene and genetic susceptibility to high myopia (HM) in the Han population of Henan Province. Methods A retrospective case-control study. From January 2021 to April 2023, 576 HM patients (HM group) and 768 healthy volunteers (control group) were recruited from the Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University. All participants were of Han ethnicity from Henan Province. SNP data for the CHRM1 gene in the Northern Han Chinese population were downloaded from the 1000 Genomes Project Online Website, with screening criteria of Hardy-Weinberg equilibrium P＞0.05 and minor allele frequency＞0.05. Haploview software was used to analyze HapMap genotypes, identifying 5 tagSNP: rs55885673, rs544978, rs56995061, rs1942499, and rs2075748. MassARRAY system was employed for genotyping the 5 tagSNP loci. The SHEsis online software was employed to analyze the distribution differences of genotypes and allele frequencies between the two groups. Linkage disequilibrium coefficient D' was used to evaluate the recombination events between SNP loci, and haplotypes with frequencies exceeding 3% were constructed for statistical analysis. Results The age of the HM group was significantly lower than that of the control group (t=18.515, P＜0.05), while no significant difference was observed in gender distribution (χ²=2.869, P=0.087). Compared with the control group, the HM group showed significantly higher frequencies of the C allele [odds ratio (OR)=1.44, 95% confidence interval (CI): 1.09-1.91, Pc=0.045)] and CC genotype (OR=1.50, 95% CI: 1.11-2.02, Pc=0.038) at the rs56995061 locus, and significantly lower frequencies of the T allele (OR=0.69, 95%CI: 0.52-0.91, Pc=0.045) and CT genotype (OR=0.67, 95%CI: 0.49-0.91, Pc=0.045). Additionally, the CT genotype frequency at the rs2075748 locus was significantly lower in the HM group (OR=0.66, 95%CI: 0.53-0.84, Pc=0.002). The haplotype G-T-A-A formed by rs55885673-rs56995061-rs1942499-rs544978 was significantly less frequent in the HM group (OR=0.71, 95%CI: 0.54-0.94, P=0.170). Conclusions The polymorphisms at the SNP loci rs56995061 and rs2075748 in the CHRM1 gene are associated with the genetic susceptibility to high myopia in the Chinese Han population. The G-T-A-A haplotype composed of rs55885673-rs56995061-rs1942499-rs544978 reduces the susceptibility to high myopia.

1.	Lee KE, Klein BE, Klein R, et al. Aggregation of refractive error and 5-year changes in refractive error among families in the Beaver Dam Eye Study[J]. Arch Ophthalmol, 2001, 119(11): 1679-1685. DOI: 10.1001/archopht.119.11.1679.
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5.	褚仁远, 王国民, 王蓉芳, 等. 双生子近视眼的研究[J]. 中华眼科杂志, 1983, 19(5): 265-268.Chu RY, Wang GM, Wang RF, et al. Study on myopia of twins[J]. Chin J Ophthalmol, 1983, 19(5): 265-268.
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9.	Gao W, Liang FM, Chen T, et al. Review of research progresses in genetics related to myopia[J]. Int Eye Sci, 2022, 22(7): 1074-1078. DOI: 10.3980/j.issn.1672-5123.2022.7.02.
10.	Ruan Y, Patzak A, Pfeiffer N, et al. Muscarinic acetylcholine receptors in the retina-therapeutic implications[J/OL]. Int J Mol Sci, 2021, 22(9): 4989[2021-05-08]. https://pubmed.ncbi.nlm.nih.gov/34066677/. DOI: 10.3390/ijms22094989.
11.	Pedersen JE, Bergqvist CA, Larhammar D. Evolution of the muscarinic acetylcholine receptors in vertebrates[J/OL]. eNeuro, 2018, 5(5): ENEURO. 0340-18.2018[2018-11-08]. https://pubmed.ncbi.nlm.nih.gov/30564629/. DOI: 10.1523/ENEURO.0340-18.2018.
12.	Wessler I, Kirkpatrick CJ. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans[J]. Br J Pharmacol, 2008, 154(8): 1558-1571. DOI: 10.1038/bjp.2008.185.
13.	McBrien NA, Jobling AI, Truong HT, et al. Expression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia[J]. Mol Vis, 2009, 15: 464-475.
14.	Kothari M, Rathod V. Efficacy of 1% atropine eye drops in retarding progressive axial myopia in Indian eyes[J]. Indian J Ophthalmol, 2017, 65(11): 1178-1181. DOI: 10.4103/ijo.IJO_418_17.
15.	Li FF, Yam JC. Low-concentration atropine eye drops for myopia progression[J]. Asia Pac J Ophthalmol (Phila), 2019, 8(5): 360-365. DOI: 10.1097/APO.0000000000000256.
16.	Yam JC, Zhang XJ, Zhang Y, et al. Effect of low-concentration atropine eyedrops vs placebo on myopia incidence in children: the LAMP2 randomized clinical trial[J]. JAMA, 2023, 329(6): 472-481. DOI: 10.1001/jama.2022.24162.
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19.	Lind GJ, Chew SJ, Marzani D, et al. Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes[J]. Invest Ophthalmol Vis Sci, 1998, 39(12): 2217-2231.
20.	Stone RA, Lin T, Laties AM. Muscarinic antagonist effects on experimental chick myopia[J]. Exp Eye Res, 1991, 52(6): 755-758. DOI: 10.1016/0014-4835(91)90027-c.
21.	Cottriall CL, McBrien NA. The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew[J]. Invest Ophthalmol Vis Sci, 1996, 37(7): 1368-1379.
22.	Cottriall CL, Truong HT, McBrien NA. Inhibition of myopia development in chicks using himbacine: a role for M(4) receptors?[J]. Neuroreport, 2001, 12(11): 2453-2456. DOI: 10.1097/00001756-200108080-00033.
23.	Tao Y, Li XL, Sun LY, et al. Effect of green flickering light on myopia development and expression of M1 muscarinic acetylcholine receptor in guinea pigs[J]. Int J Ophthalmol, 2018, 11(11): 1755-1760. DOI: 10.18240/ijo.2018.11.04.
24.	Shi YY, He L. Publisher correction: SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci[J]. Cell Res, 2023, 2023: 10. DOI: 10.1038/s41422-023-00805-3.
25.	Sabbir MG, Swanson M, Albensi BC. Loss of cholinergic receptor muscarinic 1 impairs cortical mitochondrial structure and function: implications in Alzheimer’s disease[J/OL]. Front Cell Dev Biol, 2023, 11: 1158604[2023-05-18]. https://pubmed.ncbi.nlm.nih.gov/37274741/. DOI: 10.3389/fcell.2023.1158604.
26.	Guggenheim JA, Zayats T, Hammond C, et al. Lumican and muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia[J]. Eye, 2010, 24(8): 1411-1412. DOI: 10.1038/eye.2010.55.
27.	González-Iglesias E, López-Vázquez A, Noval S, et al. Next-generation sequencing screening of 43 families with non-syndromic early-onset high myopia: a clinical and genetic study[J]. Int J Mol Sci, 2022, 23(8): 4233. DOI: 10.3390/ijms23084233.

1. Lee KE, Klein BE, Klein R, et al. Aggregation of refractive error and 5-year changes in refractive error among families in the Beaver Dam Eye Study[J]. Arch Ophthalmol, 2001, 119(11): 1679-1685. DOI: 10.1001/archopht.119.11.1679.
2. Cai XB, Shen SR, Chen DF, et al. An overview of myopia genetics[J]. Exp Eye Res, 2019, 188: 107778[2019-08-28]. https://pubmed.ncbi.nlm.nih.gov/31472110/. DOI: 10.1016/j.exer.2019.107778.
3. Xiang ZY, Zou HD. Recent epidemiology study data of myopia[J/OL]. J Ophthalmol, 2020, 2020: 4395278[2020-11-04]. https://pubmed.ncbi.nlm.nih.gov/33489329/. DOI: 10.1155/2020/4395278.
4. Huang PC, Hsiao YC, Tsai CY, et al. Protective behaviours of near work and time outdoors in myopia prevalence and progression in myopic children: a 2-year prospective population study[J]. Br J Ophthalmol, 2020, 104(7): 956-961. DOI: 10.1136/bjophthalmol-2019-314101.
5. 褚仁远, 王国民, 王蓉芳, 等. 双生子近视眼的研究[J]. 中华眼科杂志, 1983, 19(5): 265-268.Chu RY, Wang GM, Wang RF, et al. Study on myopia of twins[J]. Chin J Ophthalmol, 1983, 19(5): 265-268.
6. Williams KM, Kraphol E, Yonova-Doing E, et al. Early life factors for myopia in the British Twins Early Development Study[J]. Br J Ophthalmol, 2019, 103(8): 1078-1084. DOI: 10.1136/bjophthalmol-2018-312439.
7. Pusti D, Benito A, Madrid-Valero JJ, et al. Disparity between central and peripheral refraction inheritance in twins[J/OL]. Sci Rep, 2021, 11(1): 12196[2021-06-09]. https://pubmed.ncbi.nlm.nih.gov/34108506/. DOI: 10.1038/s41598-021-90838-8.
8. Tedja MS, Haarman AEG, Meester-Smoor MA, et al. IMI-myopia genetics report[J]. Invest Ophthalmol Vis Sci, 2019, 60(3): 89-105. DOI: 10.1167/iovs.18-25965.
9. Gao W, Liang FM, Chen T, et al. Review of research progresses in genetics related to myopia[J]. Int Eye Sci, 2022, 22(7): 1074-1078. DOI: 10.3980/j.issn.1672-5123.2022.7.02.
10. Ruan Y, Patzak A, Pfeiffer N, et al. Muscarinic acetylcholine receptors in the retina-therapeutic implications[J/OL]. Int J Mol Sci, 2021, 22(9): 4989[2021-05-08]. https://pubmed.ncbi.nlm.nih.gov/34066677/. DOI: 10.3390/ijms22094989.
11. Pedersen JE, Bergqvist CA, Larhammar D. Evolution of the muscarinic acetylcholine receptors in vertebrates[J/OL]. eNeuro, 2018, 5(5): ENEURO. 0340-18.2018[2018-11-08]. https://pubmed.ncbi.nlm.nih.gov/30564629/. DOI: 10.1523/ENEURO.0340-18.2018.
12. Wessler I, Kirkpatrick CJ. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans[J]. Br J Pharmacol, 2008, 154(8): 1558-1571. DOI: 10.1038/bjp.2008.185.
13. McBrien NA, Jobling AI, Truong HT, et al. Expression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia[J]. Mol Vis, 2009, 15: 464-475.
14. Kothari M, Rathod V. Efficacy of 1% atropine eye drops in retarding progressive axial myopia in Indian eyes[J]. Indian J Ophthalmol, 2017, 65(11): 1178-1181. DOI: 10.4103/ijo.IJO_418_17.
15. Li FF, Yam JC. Low-concentration atropine eye drops for myopia progression[J]. Asia Pac J Ophthalmol (Phila), 2019, 8(5): 360-365. DOI: 10.1097/APO.0000000000000256.
16. Yam JC, Zhang XJ, Zhang Y, et al. Effect of low-concentration atropine eyedrops vs placebo on myopia incidence in children: the LAMP2 randomized clinical trial[J]. JAMA, 2023, 329(6): 472-481. DOI: 10.1001/jama.2022.24162.
17. Ha A, Kim SJ, Shim SR, et al. Efficacy and safety of 8 atropine concentrations for myopia control in children: a network meta-analysis[J]. Ophthalmology, 2022, 129(3): 322-333. DOI: 10.1016/j.ophtha.2021.10.016.
18. Kaiti R, Shyangbo R, Sharma IP. Role of atropine in the control of myopia progression- a review[J]. Beyoglu Eye J, 2022, 7(3): 157-166. DOI: 10.14744/bej.2022.07742.
19. Lind GJ, Chew SJ, Marzani D, et al. Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes[J]. Invest Ophthalmol Vis Sci, 1998, 39(12): 2217-2231.
20. Stone RA, Lin T, Laties AM. Muscarinic antagonist effects on experimental chick myopia[J]. Exp Eye Res, 1991, 52(6): 755-758. DOI: 10.1016/0014-4835(91)90027-c.
21. Cottriall CL, McBrien NA. The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew[J]. Invest Ophthalmol Vis Sci, 1996, 37(7): 1368-1379.
22. Cottriall CL, Truong HT, McBrien NA. Inhibition of myopia development in chicks using himbacine: a role for M(4) receptors?[J]. Neuroreport, 2001, 12(11): 2453-2456. DOI: 10.1097/00001756-200108080-00033.
23. Tao Y, Li XL, Sun LY, et al. Effect of green flickering light on myopia development and expression of M1 muscarinic acetylcholine receptor in guinea pigs[J]. Int J Ophthalmol, 2018, 11(11): 1755-1760. DOI: 10.18240/ijo.2018.11.04.
24. Shi YY, He L. Publisher correction: SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci[J]. Cell Res, 2023, 2023: 10. DOI: 10.1038/s41422-023-00805-3.
25. Sabbir MG, Swanson M, Albensi BC. Loss of cholinergic receptor muscarinic 1 impairs cortical mitochondrial structure and function: implications in Alzheimer’s disease[J/OL]. Front Cell Dev Biol, 2023, 11: 1158604[2023-05-18]. https://pubmed.ncbi.nlm.nih.gov/37274741/. DOI: 10.3389/fcell.2023.1158604.
26. Guggenheim JA, Zayats T, Hammond C, et al. Lumican and muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia[J]. Eye, 2010, 24(8): 1411-1412. DOI: 10.1038/eye.2010.55.
27. González-Iglesias E, López-Vázquez A, Noval S, et al. Next-generation sequencing screening of 43 families with non-syndromic early-onset high myopia: a clinical and genetic study[J]. Int J Mol Sci, 2022, 23(8): 4233. DOI: 10.3390/ijms23084233.

Chinese Journal of Ocular Fundus Diseases

Latest ArticlesAssociation between CHRM1 gene polymorphisms and genetic susceptibility to high myopia in the Han population of Henan province

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