中国北方女性帕金森病患者与线粒体ND4基因A11084G位点的相关性研究

Correlation between A11084G in mitochondrial ND4 gene and Parkinson＇s disease in female patients from northern China

目的探究中国北方人群线粒体DNA基因编码区多态性位点与帕金森病fPDl的关联性。方法选择自2010年4月至2015年11月在中国医科大学附属第一医院神经内科就诊的中国北方汉族PD患者353例作为PD组，同期在中国医科大学附属第一医院门诊和体检中心体检的无神经退行性疾病的北方汉族健康成人389例为对照组。采用复合PCR扩增和限制性片段长度多态性（PCR-RFLP）分析方法对2组成员线粒体DNA编码区NDl基因上T4216C位点、ND2基因上A4917G位点、ND4基因上A11084G位点、tRNA （L2）基因上A12308G位点、ND5基因上A13966G位点、tRNA （Thr）基因上G15928A位点进行遗传多态性分析。结果2组成员6个遗传多态性位点和所鉴定的6种单倍型差异均无统计学意义（P〉0．05）。进一步对性别进行分层后发现．女性PD组中A11084G多态性位点等位基因G的频率和6个位点组成的单倍型频率均较对照组高，差异有统计学意义（P〈0．05）。结论6个线粒体编码区多态性位点在中国北方群体中未提示为PD的易感因子；但A11084G位点A到G的突变可能与中国北方女性群体PD发病相关。

Objective To explore the potential relationship between 6 single nucleotide polymorphisms （SNPs） of mitochondrial DNA （mtDNA） coding region and Parkinson＇s disease （PD） in northern Chinese population. Methods Samples from 353 patients with PD and 389 control participants, collected in our hospital from April 2010 to November 2015, were genotyped by multiplex polymerase chain reaction （PCR）-restriction fragment length polymorphism （RFLP） techniques. Six SNPs （T4216C within the ND1 gene, A4917G within the ND2 gene, A11084G within the ND4 gene, A12308G within the tRNA gene, A13966G within the ND5 gene, and G15928A within the tRNA gene） in mtDNA were amplified in multiplex PCR systems and subsequently genotyped by digestion with endonucleases. Results An efficient, rapid, and economical way of multiplex genotype SNPs was successfully established. No significant differences were observed in the 6 loci and corresponding haplotypes between PD and control cohorts （P〉0.05）. After stratification by gender, however, frequencies of allele 11084G and the haplotype T-A-G-A-A-G in female group with PD were all higher than those in control ones, with significant differences （P〈0.05）. Conclusions The 6 SNPs may not be susceptible factors in the northern Chinese population. The A 11084G missense mutation might be related to PD in female patients.