Association Of HTR2A And5-HTT Gene Polymorphism With The Susceptibility To Alcohol Dependence In Yunnan Yi And Miao Population

Objective:ADS is the serious social and medical problem of the world. It is a complex disorder which is influenced by physiological and pathological mechanism.But the hereditary factor plays a dominating role in the process of AD pathogenesis. The association between Central5-hydroxytryptamine (5-HT) neurotransmission and ADS has been recognized,but the results are inconsistent and conflicting and never performed in Yunnan Yi and Miao population. The aim of present study is to study the relation between the four SNPs of human HTR2A and5-HTT gene polymorphism with alcohol dependence,and to study the etiopathogenesis of ADS.Methods:According to the Diagnostic&Statistic Manuel of Mental Disorders IV,DSM-IV,we selected110Yunnan Yi and30Yunnan Miao alcohol dependent patients in Yunnan Shilin inhabited villages and Yunnan Luquan Miao minority village and330and107normal people as control group in the same period.A total of4variations(three SNPs of the HTR2A gene and5-HTTLPR of the5-HTT gene) were genotyped Yunnan Yi and Yunnan Miao individuals using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-FRLP) and PCR-DNA sequencing techniques. The results are made statistical and biological analyzing by using SPSS17.0、 SHEsis and Haploview. Results:1、 The result of single locus analysis of5-HTR2A geneThere was no significant association of rs6311(A-1438G)、 rs6313(T102C) of HTR2A gene between alcohol dependent group and control group in Yunnan Yi and Miao Population.However,rs4941570of HTR2A gene might be associated with alcohol dependent patients in Yunnan Yi and Miao Population..Significant differences in allelic frequencies were present between case group and control group in rs4941570of HTR2A gene in Yunnan Yi Population.2、 The result of single locus analysis of5-HTT geneNo significant association was observed in5-HTTLPR polymorphism of the5-HTT between alcohol dependent group and control group in Yunnan Yi and Miao Population.3、 The analysis results of haplotypes for3SNPsThe results of haplotype analysis for rs631、 rs6313and rs4941570of HTR2A gene revealed that there are8kinds of major haplotypes in Yunnan Yi and Miao Population.The total test showed there were significant differences in the HTR2A gene polymorphisms between alcoholics and controls. In Yunnan Yi Population H8(GTG) might be a dangerous factor leading to alcohol dependence,H2(ACG)might be significantly associated with increased risks of alcohol dependence. In Yunnan Miao Population H4(ATG) might be a dangerous factor leading to alcohol dependence,Hl(ACA) might be significantly associated with increased risks of alcohol dependence.4、 The analysis results of lingkage disequilibriumThere is no strong linkage disequilibrium (D’<0.8) among rs631、 rs6313and rs4941570in the Yi Population of Yunnan.There is no strong linkage disequilibrium (D’<0.8) among rs6311、 rs6313and rs4941570in the control and alcohol dependent group in the Yi Population of Yunnan. There is strong linkage disequilibrium (D’> 0.8)among rs6311、 rs6313andrs4941570in the Miao Population of Yunnan.There is strong linkage disequilibrium (D’>0.8) betweenrs6313and rs4941570in the control group of Yunnan Miao. But there is no strong linkage disequilibrium (D’>0.8) among rs6311、 rs6313and rs4941570in the alcohol dependent group.Conclusion:There was no significant association of rs6311(A-1438G)、 rs6313(T102C) of HTR2A gene between control group and AD group in Yunnan Yi and Miao Population. However,rs4941570of HTR2A gene may be associated with alcohol dependent patientsin Yunnan Yi and Miao Population.There was also no significant association of5-HTTLPR polymorphism of5-HTT genebetween control group and AD group in Yunnan Yi and Miao Population, In Yunnan Yi Population H8(GTG) might be a dangerous factor leading to alcohol dependence,H2(ACG)might be significantly associated with increased risks of alcohol dependence. In Yunnan Miao PopulationH4(ATG) might be a dangerous factor leading to alcohol dependence,Hl(ACA) might be significantly associated with increased risks of alcohol dependence. There is no strong linkage disequilibrium (D’<0.8) among rs6311、 rs6313and rs4941570in the Yi Population of Yunnan.There is strong linkage disequilibrium (D’>0.8)among rs6311、 rs6313andrs4941570in the Miao Population of Yunnan.