CNR1、GAD1和BDNF基因多态性与云南傣族男性海洛因依赖的相关性分析

Association study of CNR1, GAD1 and BDNF polymorphisms with male heroin dependence in the Dai population in Yunnan

为了探讨大麻素受体1基因(Cannabinoid receptor 1,CNR1)3个SNP位点(rs6454674、rs1049353和rs806368)、谷氨酸脱羧酶1基因(Glutamate decarboxylase 1,GAD1)3个SNP位点(rs1978340、rs3791878和rs11542313)、脑源性神经营养因子基因(Brain-derived neurotrophic factor,BDNF)2个SNP位点(rs6265和rs13306221)与云南傣族男性海洛因依赖的相关性,文章采用病例对照关联分析,建立8-SNPs复合扩增体系,应用SNaPshot方法检测165例傣族男性海洛因依赖患者和170例健康傣族男性CNR1、GAD1和BDNF基因8个SNPs位点基因型,采用SPSS17.0、Haploview4.2、PHASE2.1和MDR软件进行统计学分析。结果显示,rs13306221基因型频率在海洛因依赖组和对照组中的差异具有统计学意义(P<0.025),海洛因依赖组rs6265 A等位基因显著高于对照组(P<0.05),由rs1978340-rs3791878-rs11542313构建的T-A-C、C-C-C、C-C-T和T-C-C单体型及rs6265-rs13306221构建的A-G单体型频率在海洛因依赖组及对照组中差异具有统计学意义(P<0.05),海洛因依赖组T-A-C、C-C-T和A-G单体型频率明显高于对照组,GAD1基因rs1978340与rs3791878之间可能存在强协同的交互作用。结果表明,CNR1基因rs1049353多态性、GAD1基因rs1978340和rs11542313多态性以及BDNF基因rs6265和rs13306221多态性与云南傣族男性海洛因依赖相关联,并且携带rs6265 A等位基因的个体可能更容易对海洛因产生依赖。

In order to analyze the association of CNR1（Cannabinoid receptor 1）,GAD1（Glutamate decarboxylase 1）,and BDNF（Brain-derived neurotrophicfactor） polymorphisms with male heroin dependence in the Dai population in Yunnan Province,an eight-SNP co-amplification protocol was established to genotype on the SNaPshot platform.A case-control study was performed with 8 SNPs from CNR1,GAD1,and BDNF genes in 165 heroin-dependent males and 170 healthy males of the Dai population.Statistical analyses were conducted with SPSS17.0,Haploview4.2,PHASE2.1,and MDR software.We found that：（1） the genotype frequency of rs13306221 was significant in the case group （P〈0.025）; （2） the A allelic frequency of rs6265 was significantly higher in the case group; （3） the haplotypes of T-A-C,C-C-C,C-C-T,and T-C-C based on rs1978340-rs3791878-rsl1542313 and haplotype A-G based on rs6265-rs13306221 were significant （P〈0.05）; （4） the haplotype frequencies of T-A-C,C-C-T,and A-G were significantly higher in the case group.These results indicate that the linkage between rs1978340 and rs3791878 in GAD1 has a strong association with heroin dependence.Furthermore,polymorphisms in CNR1 （rs1049353）,GAD1 （rs1978340 and rs11542313）,and BDNF （rs6265 and rs13306221） were associated with heroin dependence in the Yunnan Dai population,and individuals with the rs6265 A allele were more likely to be heroin dependent.