帕金森病患者血清中Aβ1-42含量与MTHFRC677T基因多态性的关联性研究
|
摘要
目的探讨帕金森病(PD)患者血清β-淀粉样蛋白1-42(Aβ1-42)水平与N5,N10-亚甲四氢叶酸还原酶(MTHFR)基因多态性的关系。方法采用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)分别检测PD患者50例和正常对照组50名MTHFR基因C677T位点多态性,同时测定血清Aβ1-42水平。结果PD组MTHFR基因TT型频率为32.0%,CT型频率为52.0%,CC型频率为16.0%;对照组分别为12.0%、56.0%和32.0%。PD组T等位基因频率为60.0%,C等位基因频率为40.0%;对照组分别为42.0%和58.0%。PD组MTHFR基因TT型患者血清Aβ1-42水平显著低于其他两型(F=4.831,P=0.012),CT型血清Aβ1-42水平显著低于CC型(P <0.05)。结论 PD患者MTHFR基因C677T突变与Aβ1-42水平显著相关,MTHFR基因突变可能是引起低Aβ1-42的一个重要遗传因素。
Objective To investigate the correlation between the serum levels of β-amyloid 1-42(Aβ1-42) and polymorphisms of N5,N10-methylenetetrahydrofolate reductase(MTHFR) gene in patients with Parkinson's disease(PD).Methods The polymorphisms of MTHFRC677 T gene were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique in 50 PD patients and 50 normal controls,and their serum levels of Aβ1-42 were detected by Enzyme-linked Immunosorbent Assay(ELISA) method.Results The frequency of TT type of MTHFR gene in PD patients was 32.0%; the frequency of CT type was 52.0% and the frequency of CC type was 16.0%.The frequencies of TT type,CT type and CC type in the control group were 12.0%,56.0% and 32.0% respectively.In PD group,the frequency of T allele was 60.0% and the frequency of C allele was 40.0%.In the control group,the frequency of T allele was 42.0% and the frequency of C allele was 58.0%.The serum level of Aβ1-42 in the patients with TT type of MTHFR gene in PD group was significantly lower than that in the patients with other two types(F = 4.831,P = 0.012),and the serum level of Aβ1-42 in CT type was significantly lower than that in CC type(P < 0.05).Conclusion The MTHFR C677T gene mutations may be significantly associated with Aβ1-42 levels in patients with PD and the homozygous mutation in MTHFR gene may be an important genetic factor of lower Aβ1-42.
Objective To investigate the correlation between the serum levels of β-amyloid 1-42(Aβ1-42) and polymorphisms of N5,N10-methylenetetrahydrofolate reductase(MTHFR) gene in patients with Parkinson's disease(PD).Methods The polymorphisms of MTHFRC677 T gene were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique in 50 PD patients and 50 normal controls,and their serum levels of Aβ1-42 were detected by Enzyme-linked Immunosorbent Assay(ELISA) method.Results The frequency of TT type of MTHFR gene in PD patients was 32.0%; the frequency of CT type was 52.0% and the frequency of CC type was 16.0%.The frequencies of TT type,CT type and CC type in the control group were 12.0%,56.0% and 32.0% respectively.In PD group,the frequency of T allele was 60.0% and the frequency of C allele was 40.0%.In the control group,the frequency of T allele was 42.0% and the frequency of C allele was 58.0%.The serum level of Aβ1-42 in the patients with TT type of MTHFR gene in PD group was significantly lower than that in the patients with other two types(F = 4.831,P = 0.012),and the serum level of Aβ1-42 in CT type was significantly lower than that in CC type(P < 0.05).Conclusion The MTHFR C677T gene mutations may be significantly associated with Aβ1-42 levels in patients with PD and the homozygous mutation in MTHFR gene may be an important genetic factor of lower Aβ1-42.
引文
1刘疏影,陈彪.帕金森病流行现状[J].中国现代神经疾病杂志,2016,16(2):98-101.
2吴文波,王超,牛德旺,等.血清Aβ1-42、UA水平和血清炎症因子与帕金森病发病的相关性研究[J].中国实验诊断学,2018,22(3):484-486.
3 Nefic H,Mackic-Djurovic M,Eminovic I.The frequency of the 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase(MTHFR)gene in the population[J].Med Arch,2018,72(3):164-169.
4 Liu L,Zhang L,Guo L,et al.MTHFR C677T and A1298C polymorphisms may contribute to the risk of Parkinson's disease:A meta-analysis of 19 studies[J].Neurosci Lett,2018,662:339-345.
5中华医学会神经病学分会帕金森病及运动障碍学组,中国医师协会神经内科医师分会帕金森病及运动障碍专业委员会.中国帕金森病的诊断标准(2016版)[J].中华神经科杂志,2016,49(4):268-271.
6 Ohnishi T,Yanazawa M,Sasahara T,et al.Na,K-ATPaseα3 is a death target of Alzheimer patient amyloid-βassembly[J].Proc Natl Acad Sci U S A,2015,112(32):E4465-E4474.
7 Constantinides VC,Paraskevas GP,Emmanouilidou E,et al.CSF biomarkersβ-amyloid,tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes[J].J Neurol Sci,2017,382:91-95.
8赵明,闫雷,龚守良,等.Aβ42介导的阿尔茨海默病对小脑AMPA受体GluR2亚基及caspase-3表达的影响[J].中国老年学杂志,2018,38(10):2436-2438.
9 Rochester L,Galna B,Lod S,et al.Decrease in Aβ42 predicts dopa-resistant gait progression in early Parkinson disease[J].Neurology,2017,88(16):1501-1511.
10 Stallings NR,O'Neal MA,Hu J,et al.Pin1 mediates Aβ42-induced dendritic spine loss[J].Sci Signal,2018,11(522):eaap8734.
11周佳菁,袁箐,韩峻松,等.亚甲基四氢叶酸还原酶多态性的临床应用研究进展[J].医学综述,2018,24(7):1266-1272.
12 Stoccoro A,Tannorella P,Salluzzo MG,et al.The methylenetetrahydrofolate reductase C677T polymorphism and risk for late-onset Alzheimer's disease:Further evidence in an Italian multicenter Study[J].J Alzheimers Dis,2017,56(4):1451-1457.
13 6)Zur-Wyrozumska K,Pera J,Dziubek A,et al.Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis:Polish population study and a meta-analysis[J].Neurol Neurochir Pol,2017,51(2):135-139.
14 Yuan L,Song Z,Deng X,et al.Association of the MTHFR rs1801131and rs1801133 variants in sporadic Parkinson's disease patients[J].Neurosci Lett,2016,616:26-31.
15 Zhu Y,Zhu RX,He ZY,et al.Association of MTHFR C677T with total homocysteine plasma levels and susceptibility to Parkinson's disease:a meta-analysis[J].Neurol Sci,2015,36(6):945-951.
16 Liew SC,Gupta ED.Methylenetetrahydrofolate reductase(MTHFR)C677T polymorphism:epidemiology,metabolism and the associated diseases[J].Eur J Med Genet,2015,58(1):1-10.
17 Terrelonge M Jr,Marder KS,Weintraub D,et al.CSFβ-amyloid1-42 predicts progression to cognitive impairment in newly diagnosed Parkinson disease[J].J Mol Neurosci,2016,58(1):88-92.
18 Backstr9m DC,Eriksson Domell9f M,Linder J,et al.Cerebrospinal fluid patterns and the risk of future dementia in early,incident Parkinson disease[J].JAMA Neurol,2015,72(10):1175-1182.
2吴文波,王超,牛德旺,等.血清Aβ1-42、UA水平和血清炎症因子与帕金森病发病的相关性研究[J].中国实验诊断学,2018,22(3):484-486.
3 Nefic H,Mackic-Djurovic M,Eminovic I.The frequency of the 677C>T and 1298A>C polymorphisms in the methylenetetrahydrofolate reductase(MTHFR)gene in the population[J].Med Arch,2018,72(3):164-169.
4 Liu L,Zhang L,Guo L,et al.MTHFR C677T and A1298C polymorphisms may contribute to the risk of Parkinson's disease:A meta-analysis of 19 studies[J].Neurosci Lett,2018,662:339-345.
5中华医学会神经病学分会帕金森病及运动障碍学组,中国医师协会神经内科医师分会帕金森病及运动障碍专业委员会.中国帕金森病的诊断标准(2016版)[J].中华神经科杂志,2016,49(4):268-271.
6 Ohnishi T,Yanazawa M,Sasahara T,et al.Na,K-ATPaseα3 is a death target of Alzheimer patient amyloid-βassembly[J].Proc Natl Acad Sci U S A,2015,112(32):E4465-E4474.
7 Constantinides VC,Paraskevas GP,Emmanouilidou E,et al.CSF biomarkersβ-amyloid,tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes[J].J Neurol Sci,2017,382:91-95.
8赵明,闫雷,龚守良,等.Aβ42介导的阿尔茨海默病对小脑AMPA受体GluR2亚基及caspase-3表达的影响[J].中国老年学杂志,2018,38(10):2436-2438.
9 Rochester L,Galna B,Lod S,et al.Decrease in Aβ42 predicts dopa-resistant gait progression in early Parkinson disease[J].Neurology,2017,88(16):1501-1511.
10 Stallings NR,O'Neal MA,Hu J,et al.Pin1 mediates Aβ42-induced dendritic spine loss[J].Sci Signal,2018,11(522):eaap8734.
11周佳菁,袁箐,韩峻松,等.亚甲基四氢叶酸还原酶多态性的临床应用研究进展[J].医学综述,2018,24(7):1266-1272.
12 Stoccoro A,Tannorella P,Salluzzo MG,et al.The methylenetetrahydrofolate reductase C677T polymorphism and risk for late-onset Alzheimer's disease:Further evidence in an Italian multicenter Study[J].J Alzheimers Dis,2017,56(4):1451-1457.
13 6)Zur-Wyrozumska K,Pera J,Dziubek A,et al.Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis:Polish population study and a meta-analysis[J].Neurol Neurochir Pol,2017,51(2):135-139.
14 Yuan L,Song Z,Deng X,et al.Association of the MTHFR rs1801131and rs1801133 variants in sporadic Parkinson's disease patients[J].Neurosci Lett,2016,616:26-31.
15 Zhu Y,Zhu RX,He ZY,et al.Association of MTHFR C677T with total homocysteine plasma levels and susceptibility to Parkinson's disease:a meta-analysis[J].Neurol Sci,2015,36(6):945-951.
16 Liew SC,Gupta ED.Methylenetetrahydrofolate reductase(MTHFR)C677T polymorphism:epidemiology,metabolism and the associated diseases[J].Eur J Med Genet,2015,58(1):1-10.
17 Terrelonge M Jr,Marder KS,Weintraub D,et al.CSFβ-amyloid1-42 predicts progression to cognitive impairment in newly diagnosed Parkinson disease[J].J Mol Neurosci,2016,58(1):88-92.
18 Backstr9m DC,Eriksson Domell9f M,Linder J,et al.Cerebrospinal fluid patterns and the risk of future dementia in early,incident Parkinson disease[J].JAMA Neurol,2015,72(10):1175-1182.