HDAC2基因多态性与汉族男性酒精使用障碍的关联性

The correlation of HDAC2 polymorphisms with alcohol use disorder in male people of Han nationality

目的探究组蛋白去乙酰化酶2(histone deacetylase 2,HDAC2)基因多态性与汉族男性酒精使用障碍(alcohol use disorder,AUD)之间的关联性,为早期识别和干预酒精使用障碍提供参考。方法选择194例汉族AUD患者(病例组)和310例正常人(对照组),提取两组外周血基因组DNA,从HapMap数据库获得HDAC2基因的13个SNP位点,采用Agena MassARRAY SNP基因分型法对两组进行基因分型。SPSS 25.0分析两组基因型频率和等位基因频率的差异,并使用Haploview 4.2软件进行连锁不平衡以及单倍体分析,利用置换次数为50000次的置换检验进行多重检验矫正。结果HDAC2基因3个SNP位点(rs9481408,rs6568819,rs9488289)的基因型在病例组和对照组之间均差异有统计学意义(均P<0.05)。进一步在5种不同遗传模型中分析这3个位点,结果显示病例组与对照组相比,三个位点在隐性遗传模式下与AUD存在显著相关(P=0.033,T/T与C/C-C/T基因型比较,OR=1.78,95%CI:1.05~3.03;P=0.032,T/T与C/C-C/T基因型比较,OR=1.79,95%CI:1.05~3.03;P=0.022,G/G与C/C-C/G基因型比较,OR=1.85,95%CI:1.09~3.13)。构建7个SNP单倍型,其中GATCTGCCAATAA在病例组和对照组之间关联比值比为2.44,差异有统计学意义(P<0.05)。结论HDAC2基因多态性位点rs9481408、rs6568819、rs9488289以及GATCTGCCAATAA单倍型与汉族男性人群酒精使用障碍的发病具有相关性,HDAC2基因是AUD易感基因之一。

Objective To explore the association between polymorphism of Histone Deacetylase 2(HDAC2)gene and alcohol use disorder(AUD)in male people of Han nationality for seeking suitable single nucleotide loci(SNP),and provide reference for early diagnosis and intervention of alcohol use disorder(AUD).Methods A total of 194 male AUD patients of Han nationality(case group)and 310 normal men of Han nationality(control group)were selected for the study.The genomic DNA of peripheral blood of the subjects in the two groups was extracted,and 13 SNP loci of HDAC2 gene were obtained from HapMap database.The subjects in the two groups were genotyped by Agena MassARRAY SNP genotyping method.SPSS 25.0 was used to statistically analyze the differences of genotype frequency and allele frequency between the two groups,and Haploview 4.2 software was used for linkage disequilibrium and haploid analysis.The multiple test correction was carried out by the replacement test with 50000 replacement times.Results The genotype frequency of the 3 SNP loci(rs9481408,rs6568819,rs9488289)of HDAC2 gene were statistically significant different between the case group and the control group(all P<0.05).Further analysis found that the three loci were significantly correlated with AUD in the recessive genetic model between case group and control group(T/T vs C/C-C/T:OR=1.78,95%CI:1.05-3.03,P=0.033;T/T vs C/C-C/T:OR=1.79,95%CI:1.05-3.03,P=0.032;G/G vs C/C-C/G:OR=1.85,95%CI:1.09-3.13,P=0.022).Seven SNP haplotypes were constructed and the association odds ratio of GATCTGCAATAA between the case group and control group was 2.44,and the difference was statistically significant(P<0.05).Conclusion The SNP loci rs9481408,rs6568819,rs9488289 in the HDAC2 gene and haplotype GATCTGCCAATAA are associate with AUD in male people of Han nationality.These results indicated that the HDAC2 gene is one of the susceptibility genes of AUD.