CAJ | 학술논문

目的研究5,10亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与帕金森病(PD)患者伴发高同型半胱氨酸血症(H Hcy)的关系. 方法收集2011年5月至2013年3月在我院神经内科住院及门诊的PD患者161例作为PD组,同期在我院体检中心健康体检者240例作为对照组,对两组C677T多态性进行基因分型,测定患者同型半胱氨酸(Hcy)、叶酸、维生素B12水平,比较C677T多态性基因型与等位基因在PD组和对照组间分布规律；同时通过进行不同Hcy水平患者不同遗传模型分析和Logistic回归模型校正,综合研究C677T多态性与PD患者伴发HHcy的关系.结果 PD组与对照组C677T位点的基因型及等位基因的分布差异均无统计学意义(x2=0.21、0.14,P=0.901、0.710)；对PD组按Hcy水平进行分层分析结果显示,基因型及等位基因在HHcy组和Hcy正常组的频率分布差异有统计学意义(x2=11.32、6.74,P=0.003、0.009).比较HHcy组和Hcy正常组C677T多态性的分布结果显示,隐性模型下TT型和CT+ CC型频率分布差异有统计学意义(x2 =11.15,P=0.001);在纯合子模型下,CC型与TT型分布差异有统计学意义(x2=6.02,P=0.014).Logistic回归分析校正年龄、性别、叶酸、维生素B12、左旋多巴治疗情况等混杂因素后,C677T多态性的T等位基因隐性模型、纯合子模型是PD患者发生HHcy的危险因素(OR=6.83、6.86,P=0.001、0.006). 结论 MTHFR基因C677T多态性与PD发病可能不相关,但C677T多态性的T等位基因可能是PD伴发HHcy的独立危险因素.
목적 연구5,10아갑기사경협산환원매(MTHFR)기인C677T다태성여파금삼병(PD)환자반발고동형반광안산혈증(H Hcy)적관계. 방법 수집2011년5월지2013년3월재아원신경내과주원급문진적PD환자161례작위PD조,동기재아원체검중심건강체검자240례작위대조조,대량조C677T다태성진행기인분형,측정환자동형반광안산(Hcy)、협산、유생소B12수평,비교C677T다태성기인형여등위기인재PD조화대조조간분포규률；동시통과진행불동Hcy수평환자불동유전모형분석화Logistic회귀모형교정,종합연구C677T다태성여PD환자반발HHcy적관계.결과 PD조여대조조C677T위점적기인형급등위기인적분포차이균무통계학의의(x2=0.21、0.14,P=0.901、0.710)；대PD조안Hcy수평진행분층분석결과현시,기인형급등위기인재HHcy조화Hcy정상조적빈솔분포차이유통계학의의(x2=11.32、6.74,P=0.003、0.009).비교HHcy조화Hcy정상조C677T다태성적분포결과현시,은성모형하TT형화CT+ CC형빈솔분포차이유통계학의의(x2 =11.15,P=0.001);재순합자모형하,CC형여TT형분포차이유통계학의의(x2=6.02,P=0.014).Logistic회귀분석교정년령、성별、협산、유생소B12、좌선다파치료정황등혼잡인소후,C677T다태성적T등위기인은성모형、순합자모형시PD환자발생HHcy적위험인소(OR=6.83、6.86,P=0.001、0.006). 결론 MTHFR기인C677T다태성여PD발병가능불상관,단C677T다태성적T등위기인가능시PD반발HHcy적독립위험인소.
Objective To study the association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and Parkinson' s disease (PD) combined with hyperhomocysteinemia(HHcy).Methods Based on high-resolution melting(HRM) curve analysis,240 health controls (control group) and 161 patients with Parkinson's disease(case group) were genotyped for C677T polymorphism.The levels of plasma homocysteine(Hcy),folateand vitamin B12 were determined.The C677T polymorphism distribution was compared between case and control groups.The patients in case group were stratified by homocysteine level:≥15μmol/L was considered as hyperhomocysteinemia(HHcy group),and＜ 15 μmol/L was considered as normal homocysteine level(normal Hcy group).The frequency distribution of C677T genotypes and alleles were compared between the two subgroups.By means of different genetic model and logistic regression analysis,a comprehensive analysis of association was conducted between C677T genotypes and PD patients with HHcy.Results There were no significant differences in MTHFR gene C677T alleles and genotypes between case and control groups(x2 =0.21 and 0.14,both P＞0.05).When stratified by Hcy level,the frequency distributions of C677T alleles and genotypes were significantly different between HHcy group and normal Hcy group(x2=11.32 and 6.74,both P＜0.01).There were significant differences in the frequency distributions of TT and CT + CC genotypes in recessive model and CC and TT genotypes in homozygous model between HHcy group and normal Hcy group(x2 =11.15 and 6.02,P ＜0.01 or 0.05).After adjusting for confounding factors including age,sex,L-Dopa treatment,folate and vitamin B12 levels,logistic regression analysis showed that the C677T polymorphism of T alleles in recessive and homozygous models was the risk factor for HHcy in PD patients(OR=6.83 and 6.86,both P＜0.01).Conclusions There is no association between MTHFR gene C677T polymorphism and PD.However,T allele may be an independent risk factor for hyperhomocysteinemia in PD patients.