RESUMEN
Objective:To investigate the relationship between rs2075748 and rs542269 single nucleotide polymorphisms of cholinergic muscarinic receptor 1 (CHRM1)gene and susceptibility of childhood asthma, as well as the differences of pulmonary function and serum acetylcholine(Ach)levels among different genotypes.Methods:A total of 156 asthmatic children who were treated in the outpatient or hospitalized in the General Hospital of the Northern Theater Command from September 2018 to September 2020 were selected as the case group, while 134 non-asthmatic children who had a healthy physical examination were selected as the control group.The SNaPshot SNP typing technique was used to analyze the genotype of the CHRM1 gene rs2075748 and rs542269 of the study subjects.Serum Ach level was detected by double antibody sandwich method, and the pulmonary function of the case group was detected.Results:After analyzing the CHRM1 gene polymorphism, it was found that the CC, CT, and TT genotype frequencies at rs2075748 were 65.4%, 28.8%, 5.8% in the case group, and 62.8%, 32.4%, 4.8% in the control group.The C and T allele frequencies were 79.8% and 20.2% in the case group, 74.3% and 25.7% in the control group.There were no significant difference in the genotype and allele frequency distribution between the two group ( χ2=2.688, 2.530, both P>0.05), and there were no significant difference in the recessive and dominant modes between the two groups ( χ2=0.338, 2.686, both P>0.05). The TT and CT genotype frequencies at rs542269 locus were 72.4% and 27.6% in the case group, 62.7% and 37.3% in the control group.The T and C allele frequency were 86.2% and 13.8% in the case group, 81.3% and 18.7% in the control group.The genotype and allele frequency distribution were not obvious different between the two group ( χ2=3.145, 2.544, both P>0.05). The risk of asthma with variant CT and TT at rs2075748 locus of CHRM1 gene were not statistically different from that of wild-type CC (both P>0.05), and the risk of asthma with variant CT at rs542269 locus was no different from that of wild-type TT ( P>0.05). The difference in FEF50% Pred and FEF75% Pred of different genotypes at rs2075748 were statistically significant( F=3.118, 4.808, both P<0.05), wild-type CC was lower than variant CT(both P<0.05). There were no statistically significant difference in pulmonary function among different genotypes at rs542269 (both P>0.05). There was significant difference in serum Ach level between different genotypes of rs2075748 ( F=4.716, P<0.05), variant CT was lower than wild-type CC ( P<0.05), variant TT was lower than wild-type CC ( P<0.05), while no significant difference was find between variant CT and TT ( P>0.05). There was no significant difference in serum Ach level between different genotypes of rs542269 ( P>0.05). Conclusion:The rs2075748 locus of CHRM1 gene is not susceptible to asthma, but it may be related to the small airway function of asthmatic children, besides there are differences in serum Ach levels with different genotypes, and the variant serum Ach level is lower.The rs542269 locus is not a susceptibility site for asthma, and there are no difference in pulmonary function and serum Ach levels in asthmatic children with different genotypes.
RESUMEN
The autonomic nervous system contributes to prostate cancer proliferation and metastasis. However, the exact molecular mechanism remains unclear. In this study, muscarinic acetylcholine receptor M1 (CHRM1) expression was measured via immunohistochemical analysis in human prostate cancer tissue array slides. PC-3, LNCaP, and A549 cells were treated with pirenzepine or carbachol, and the cell migration and invasion abilities were evaluated. Western blotting and quantitative real-time PCR were performed to measure GLI family zinc finger 1 (GLI1), patched 1 (PTCH1), and sonic hedgehog (SHH) expression levels. High expression of CHRM1 was found in early-stage human prostate cancer tissues. In addition, the selective CHRM1 antagonist pirenzepine inhibited PC-3, LNCaP, and A549 cell migration and invasion, but the agonist carbachol promoted the migration and invasion of these three cell lines. Muscarinic signaling can be relayed by hedgehog signaling. These data show that CHRM1 is involved in the regulation of prostate cancer migration and invasion through the hedgehog signaling pathway.
RESUMEN
The autonomic nervous system contributes to prostate cancer proliferation and metastasis. However, the exact molecular mechanism remains unclear. In this study, muscarinic acetylcholine receptor M1 (CHRM1) expression was measured via immunohistochemical analysis in human prostate cancer tissue array slides. PC-3, LNCaP, and A549 cells were treated with pirenzepine or carbachol, and the cell migration and invasion abilities were evaluated. Western blotting and quantitative real-time PCR were performed to measure GLI family zinc finger 1 (GLI1), patched 1 (PTCH1), and sonic hedgehog (SHH) expression levels. High expression of CHRM1 was found in early-stage human prostate cancer tissues. In addition, the selective CHRM1 antagonist pirenzepine inhibited PC-3, LNCaP, and A549 cell migration and invasion, but the agonist carbachol promoted the migration and invasion of these three cell lines. Muscarinic signaling can be relayed by hedgehog signaling. These data show that CHRM1 is involved in the regulation of prostate cancer migration and invasion through the hedgehog signaling pathway.