摘要
目的探讨反复发作抑郁症(recurrent major depressive disorder,RMDD)与5-羟色胺1A受体(5-hydroxytryptamine 1A receptor,5-HTR1A)和5-羟色胺2A受体(5-hydroxytryptamine 2A receptor,5-HTR2A)基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)的关系。方法选取5-HTR1A(rs878567)和5-HTR2A(rs1328683、rs17068986、rs9534495)基因的4个标签SNPs(tagging SNPs,tagSNPs),使用Sequenom质谱分析对1030例RMDD患者(病例组)和851名健康对照(对照组)的DNA样本进行基因分型检测,采用关联分析和广义多因子降维法(generalized multifactor dimensionality reduction,GMDR)分析RMDD与4个tagSNPs的关系。结果5-HTR2A rs17068986基因型(=8.727,P=0.013)及等位基因(=4.955,P=0.025)频率在两组间分布差异均具有统计学意义;病例组T等位基因频率高于对照组(55.3%vs.51.6%,OR=1.158,95%CI:1.018~1.318)。5-HTR2A rs17068986基因型分布最符合显性遗传模型(P=0.003),病例组TT+TC基因型频率高于对照组(81.0%vs.75.4%,OR=1.410,95豫CI:1.120~1.760)。GMDR分析显示四阶交互模型(rs878567、rs1328683、rs17068986、rs9534495)为最优模型(P=0.001,1000次置换检验),交叉验证一致性为10/10,检验精确度为0.534。结论5-HTR2A rs17068986可能存在或连锁RMDD的易感位点,5-HTR1A和5-HTR2A基因的交互作用也与RMDD的发病有一定关系。
铱Objective To explore the association between recurrent major depressive disorder(RMDD)and single nucleotide polymorphisms(SNPs)of 5-hydroxytryptamine 1A receptor(5-HTR1A)and 5-hydroxytryptamine 2A receptor(5-HTR2A)gene.Methods Genotyping of four tagging SNPs(tagSNPs)of 5-HTR1A(rs878567)and 5-HTR2A(rs1328683,rs17068986,rs9534495)gene was performed on the samples from 1030 RMDD patients(case group)and 851 healthy volunteers(control group)using Sequenom mass spectrometry.Correlation analysis and generalized multifactor dimensionality reduction(GMDR)were used to analyze the relationship between RMDD and four tagSNPs.Results Significant differences in genotype(=8.727,P=0.013)and allele frequency(=4.955,P=0.025)distributions between cases and controls were confirmed at locus 5-HTR2A rs17068986.The frequency of T allele was higher in case group than in control group(55.3%vs.51.6%,OR=1.158,95%CI:1.018~1.318).The dominant genetic model was the best in genotype distribution of 5-HTR2A rs17068986(P=0.003)and the frequency of TT+TC genotype was higher in case group than in control group (81.0% vs. 75.4% , OR =1.410, 95%CI: 1.120 ~1.760). Generalized multifactor dimensionality reduction (GMDR) model analysis showed that four -locus interaction model (rs878567, rs1328683,rs17068986, rs9534495) was the best model (P=0.001, 1000 permutation tests, the cross-validation consistency was 10/10,and the test accuracy was 0.534). Conclusion 5-HTR2A rs17068986 may exit or link to the susceptibility sites of RMDD and the interaction between 5-HTR1A and 5-HTR2A gene is also related with RMDD.
作者
姚静
庞剑月
何瑾
冯婷婷
张淑绮
李恒芬
YAO Jing;PANG Jianyue;HE Jin;FENG Tingting;ZHANG Shuqi;LI Hengfen(The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2020年第1期13-18,共6页
Chinese Journal of Nervous and Mental Diseases
基金
国家自然科学基金项目(编号:81371494)
关键词
反复发作抑郁症
5-羟色胺受体
标签
SNPS
广义多因子降维法
Recurrent major depressive disorder
5 -hydroxyteyptamine receptor (5 -HTR)
TagSNPs Generalized multifactor dimensionality reduction (GDMR)
