多巴胺代谢酶基因多态性与帕金森病遗传易患性的相关性研究

Correlation between the genetic polymorphism of dopamine metabolic enzymes and the genetic susceptibility of Parkinson's disease

目的探讨参与多巴胺代谢的儿茶酚胺氧位甲基转移酶(COMT)基因G1947→A位点突变所致的基因多态性、NAD(P)H醌氧化还原酶基因〔NAD(P)H:quinoneoxidoreductase,NQO1〕cDNA609C→T多态性与帕金森病(PD)遗传易患性的关系。方法用PCRRFLP分析COMT、NQO1基因多态性。结果COMT基因型分布频率在PD和对照组之间差异有显著意义(P=0.045)。和对照组比较,PD组野生型(G/G)和突变型纯合子(A/A)的频率分布有增高趋势,而杂合子基因型(G/A)的分布则有降低趋势。NQO1基因T等位基因频率PD组(52%)高于正常对照组(43%)。含T碱基的NQO1基因型频率PD组显著高于正常对照组(P<0.05),其患PD的相对危险度(OR)为3.8。在COMT基因型为G/G基因型的个体,带有T碱基的NQO1基因型在PD组占91.2%,对照组占64.4%,其患PD的OR值为5.7(P=0.001)。结论CCOMT基因的G/G和A/A基因型、NQO1基因的T等位基因都是PD的危险因素。CCOMT基因的G/G基因型与NQO1基因的T等位基因的基因型可相互协同,增加PD发生的风险。

Objectives To investigate whether Parkinson's disease (PD) is associated with genetic polymorphism of catechol-O-methyltransferase (COMT) gene caused by the point mutation G1947 to A in exon 4 and NAD(P)H:quinoneoxidoreductase (NQO1) gene caused by the point mutation of cDNA609 C to T. Methods The gene polymorphisms of COMT and NQO1 was analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results There was significant difference in genotypical distribution of COMT between PD and controls (P<0.05). Both the frequencies of homozygotes for wild type G/G and mutant A/A were higher in PD comparing than those in controls. The distribution of heterozygote genetype G/A had decrease tendency in PD. Frequency of T allele of NQO1 gene was 43% and 52 % in controls and PD, respectively, with significant difference between the two groups (P<0.05), which had 3.8 of odds ratio (OR) for incidence of PD. NQO1 in G/G genetype in COMT having T allele in PD accounted for 91.2%, that in controls 64.4% with 5.7 of OR for incidence of PD. Conclusions G/G and A/A homozygote of COMT gene and T allele of NQO1 gene might be risk factors of PD, by combination of which could increase the risk of PD.