Genetic Variants Within CACNA1C Are Associated With Risk Of Insomnia In Chinese Han Population

[Background and purpose] GWAS studies abroad show that the single nucleotide polymorphism(SNP)of the loci on intron 3 and intron 9 of the CACNA1 C gene is related to insomnia and the single nucleotide polymorphism of the gene whether increase the susceptibility to insomnia in the Chinese Han population is unknown.In addition,in view of the important role of exons and 3'untranslated region(3'UTR),this study first explored the correlation between the single nucleotide polymorphism of the loci on introns,exons,and 3'UTR and the susceptibility to insomnia in the Chinese Han population,and provides a basis for the study of the etiology of insomnia in china.?Method? Case-control study was conducted.205 patients who were diag nosed with insomnia were selected in the sleep medical center and 154 healthy Chinese Han populations collected from the Second Aff iliated Hospital of University of South China from July 2016 to De cember 2018.Screened 25 tap SNPs of CACNA1 C gene through NC BI(https://www.ncbi.nlm.nih.gov/)and GWAS study abroad.Genoty ping concerning 21 tap SNPs was carried out using Matrix assisted l aser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS).Genotypes and alleles frequencies were compared among t wo groups.Rank test was performed using SPSS22.0 statistical soft ware.Haploview 4.2 software was used to detect linkage disequilibr ium analysis and haplotype analysis.?Result? 1.In Chinese Han population,the 21 locus in CACNA1 C of our study are SNPs.2.The result of CACNA1 C polymorphisms : 1)Genotype TT,TC,CC of rs2302729 located in intron 9 was statistically significant between the two groups(P=0.019),and compare the frequency distribution of genotype(CC+CT)with genotype TT was statistically significant between the two groups(P=0.005,OR=2.410,95%CI[1.283~4.526]);Compare the frequency distribution of allele C with allele T was statistically significant between the two groups(P=0.023,OR=1.426,95%CI[1.049 ~1.938]).2)Genotype AA,AG,GG of rs1051375 located in exon was statistically significant between the two groups(P=0.041),and compare the frequency distribution of genotype(AA+AG)with genotype GG was statistically significant between the two groups(P=0.013,OR= 2.715,95%CI[1.165~4.064]);Compare the frequency distribution of allele A with allele G was statistically significant between the two groups(P=0.031,OR=1.404,95%CI[1.032~1.909]).3)Genotype TT,TC,CC of rs216008 located in exon was statistically significant between the two groups(P=0.041),and compare the frequency distribution of genotype(CC+CT)with genotype TT was statistically significant between the two groups(P=0.008,OR=2.455,95%CI[1.246 ~ 4.836]);But the frequency distribution of rs216008 between the two groups was not statistically significant(P ? 0.05).The frequency distribution of other loci were not statistically significant.3.We found that the SNPs in the CACNA1 C gene showed str ong linkage(r 2>0.8):rs2302729-rs1051375;rs7316264-rs12809807-rs10466907-rs4765975-rs7957163;rs7316184-rs7304986-rs7301906-r s16929275-rs16927276-rs2051990.Specifically,two LD blocks(rs2302729-rs1051375;rs7316264-rs12809807-rs10466907-rs4765975-rs7957163)were detected.4.The rs2302729-rs1051375 CA and TG haplotypes conferred risk of insomnia in Chinese Han population(P < 0.05).?Conclusion? 1.We report here for the first time that CACNA1 C gene exon SNPs rs1051375 and rs216008 have an increased susceptibility to insomnia,while 3'UTR SNPs have no relationship with insomnia.2.Which our study found is different from the GWAS study aboard,only the SNP rs2302729 located in intron 9 was associated with insomnia in Chinese Han population.