Association Of HTR2A And 5-HTT Gene Polymorphism With The Susceptibility To Alcohol Dependence In Yunnan Han Population

Objective:Alcohol dependence (AD)is a complex disorder which is influenced by many factors.Studies indicate that hereditary factor plays a dominating role in the process of AD pathogenesis.There have been many research reports regarding the association between HTR2A and 5-HTT gene polymorphisms and AD, but the results are inconsistent and conflicting and never performed in Yunnan Han population. The aim of present study is to study the relation between the six SNPs of human HTR2A and 5-HTT gene polymorphism with alcohol dependence,and to study the etiopathogenesis of AD.Methods:According to the DSM-IV diagnostic criteria, we selected 118 alcohol dependent patients of Mental Health Center of Yunnan Province and 218 normal people as control group in the period during 2006-2010.A total of 7 variations(six SNPs of the HTR2A gene and 5-HTTLPR of the 5-HTT gene) were genotyped in 336 Yunnan Han individuals using PCR-RFLP and DNA sequencing techniques. The results are made statistical and biological analyzing by using SPSS 16.0,SHEsis and Arlequin 3.01.Results:1,The result of single locus analysisThere was no significant association of rs6311(A-1438G),rs6313(T102C),rs2296972,rs4941570 and rs4941571 of HTR2A gene between alcohol dependent group and control group in Yunnan Han Population.However,5-HTTLPR polymorphism of the 5-HTT gene might be associated with alcohol dependent patients. Significant differences in genotype frequencies were present between case group and control group of 5-HTTLPR.The proportion of LL and LS genotype was significantly smaller in case group than that was in control group.No significant association was observed in allelic frequencies, which differed in the different ethnic groups.2,The analysis results of combined haplotypesWhen SL of 5-HTTLPR combined with AA of rs6311,or TT of rs6313,or CC of rs4941571,the sick risk would be decreased, When SS of 5-HTTLPR combined with GG of rs6311, or AA of rs4941570,the sick risk would be increased.The results suggested there is a synergistic gene-gene interaction between 5-HTTLPR and HTR2A gene in the pathogenesis of AD.3,The analysis results of haplotypes for 5 SNPsThe results of haplotype analysis for rs6311,rs6313,rs2296972,rs4941570 and rs4941571 of HTR2A gene revealed that there are 11 kinds of major haplotypes in Yunnan Han Population.The total test showed there were significant differences in the HTR2A gene polymorphisms between alcoholics and controls. H6 (GCTGC) might be a dangerous factor leading to alcohol dependence,H8 (ATGGC) might be significantly associated with increased risks of alcohol dependence.4,The analysis results of lingkage disequilibriumLingkage disequilibrium analysis showed that there were strong linkages between rs631,rs6313,rs4941570 and rs4941571 in Yunnan Han Population. (D' >0.8).Conclusion:There was no significant association of rs6311(A-1438G) rs6313(T102C),rs2296972,rs4941570 and rs4941571 of HTR2A gene between AD group and control group in Yunnan Han Population. However,5-HTTLPR polymorphism of 5-HTT gene may be associated with alcohol dependent patients, and the genotype LL or LS may be a genetic factor that responsible for decreasing susceptibility of AD in Yunnan Han population.There is a synergistic gene-gene interaction between 5-HTTLPR and HTR2A gene in the pathogenesis of AD.H6 (GCTGC) might be a dangerous factor leading to AD,H8 (ATGGC) might be significantly associated with increased risks of AD.There were strong linkages between rs6311,rs6313,rs4941570 and rs4941571 in Yunnan Han Population. (D >0.8).