Association Between 5-hydroxytryptamine Transporter (5-HTT) Gene And Primary Insomnia Sleep Phenotype

Objective:Studies have shown that primary insomnia(PI)has genetic characteristics,serotonin(5-hydroxy tryptamine,5-HT)is involved in sleep regulation,and 5-HT transporter(5-HTT)pair The function of 5-HT plays a key role.This paper discusses the correlation between 6 sites(rs2020936,rs3794808,rs140700,rs6352,5-HTTLPR,STin2 VNTR)and PI on the 5-HTT gene polymorphism from the genomic level.In order to obtain the genetic information data of the population related to primary insomnia,it will lay a foundation for the future construction of PI-related genetic information database,and the 5-HTT gene polymorphism detection as an important clinical indicator for PI diagnosis and treatment.Methods:In this study,a total of 112 peripheral blood samples from PI patients and healthy controls were collected,and the whole genome DNA of all samples collected was extracted.The 5-HTT gene functional SNPs were selected using HapMap,NCBI and other websites and databases,and 6 were selected.Rs2020936,rs3794808,rs140700,rs6352,5-HTTLPR,STin2 VNTR)polymorphism sites were studied;flight mass spectrometry was used for primer synthesis,PCR amplification,genotyping and sequencing verification;using SPSS20.0 software The results of genotyping were statistically analyzed,and the data were subjected to linkage disequilibrium analysis and haplotype analysis using online SHEsis software.Results:1.Analysis of clinical sample characteristicsIn clinical baseline data such as age(?~2=2.730,P=0.009),body weight(?~2=0.673,P=0.504),and years of education(?~2=-0.355,P=0.724),There was not significantly Statistical difference between the PI group and control group(P>0.05).There were obviously differences between the two groups in the ISI,PSQI,BDI,and STAI scales,Above information has statistically significant(P<0.05).2.SNP site Hardy-Weinberg(HWE)balance detectionThe HWE balance test showed that there was no difference between the two groups in terms of observed values and expected values,and there was not blatantly statistical(P>0.05),that is,both groups met the HWE rule.3.Association analysis between single SNP locus and primary insomniaThere was not apparently difference between PI group and Control group of rs2020936 locus on 5-HTT gene.(P=0.830,OR=0.912,95%CI=0.394-2.113);there was no obviously difference of rs3794808 locus on 5-HTT between PI group and Control group(P=0.443,OR=0.566,95%CI=0.130-2.462);the difference of rs140700locus on 5-HTT gene in PI group and Control group was not apparently meaning(P=0.469,OR=0.703,95).%CI=0.270-1.831);there was not blatantly statistical discrimination of rs6352 locus on 5-HTT gene between PI group and Control group(P=0.554,OR=2.043,95%CI=0.179-23.292);the discrimination of 5-HTTLPR locus on 5-HTT gene between the PI group and the Control group was not statistically significant.(P=0.659,OR=0.878,95%CI=00.494-1.563);there was not manifestly disparity between the PI group and the Control group of STin2 VNTR locus(P=0.715,OR=1.236,95%CI=0.395-3.867).4.Gene linkage disequilibrium analysisThere is a linkage disequilibrium between the six sites on the 5-HTT gene(rs2020936,rs3794808,rs140700,rs6352,5-HTTLPR,STin2 VNTR),of which rs140700 and rs6352(D'=1.000),rs2020936 and rs6352(D'There is a complete linkage disequilibrium between=1.000);rs2020936 and rs3794808(D'=0.942),rs3794808 and rs6352(D'=0.980),rs6352 and 5-HTTLPR(D'=0.997),rs6352 and STin2 VNTR(D'There is a strong linkage diseq uilibrium between=0.999);there is a moderate linkage disequilibrium between rs140700 and rs2020936(D'=0.687).5.Gene haplotype analysisTwenty haplotypes were constructed on these 6 sites on the 5-HTT gene,and the haplotype of C G C T L 12 was statistically significant in the PI group and the Control group(P=0.041).6.Analysis of some genotypes and clinical psychological characteristicsGroup C and group T(rs140700);group C and group T(rs3794808);group S and group L(5-HTTLPR);group 10 and group 12(STin2 VNTR)had no difference in total scores of depression and anxiety scale Statistical significance(P>0.05).Conclusion:1.The 5-HTT gene polymorphism site has no correlation with genotype and allele frequency in primary insomnia,and it is necessary to continue to explore its correlation with the disease by expanding the sample size.2.This study found that the haplotype of the 5-HTT gene haplotype was statistically significant in the PI group and the control group(P=0.041).This haplotype can increase the insomnia of the group.risk.3.Gene linkage disequilibrium analysis found that there is a strong linkage disequilibrium between rs2020936 and rs3794808,rs3794808 and rs6352,rs6352 and 5-HTTLPR,rs6352 and STin2 VNTR.The above gene loci ma y increase the risk of primary insomnia.It is speculated that the gene may be related to primary insomnia,and the subsequent confirmation is to be further confirmed after expanding the sample size.4.Four sites(rs140700,rs3794808,5-HTTLPR,STin2 VNTR)have not been found to be associated with anxiety and depression in PI patients,suggesting that our selected SNP sites may not be associated with anxiety and depression in patients with primary insomnia.