The COMT L allele modifies the association between MAOB polymorphism and PD in Taiwanese

被引:67
作者
Wu, RM
Cheng, CW
Chen, KH
Lu, SL
Shen, DE
Ho, YF
Chern, HD
机构
[1] Natl Taiwan Univ Hosp, Dept Neurol, Taipei 100, Taiwan
[2] Natl Taiwan Univ, Coll Med, Dept Neurol, Taipei 10018, Taiwan
[3] Natl Taiwan Univ, Coll Med, Grad Inst Pharmaceut Sci, Taipei 10018, Taiwan
[4] Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol, Taipei 10764, Taiwan
[5] Vet Gen Hosp, Neurol Inst, Taipei, Taiwan
[6] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan
关键词
D O I
10.1212/WNL.56.3.375
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: Reports suggest that catechol-O-methyltransferase (COMTL/L) (Val(158)/Met) and monoamine oxidase B (MAOB) intron 13 genotype polymorphism is associated with PD. To understand the ethnicity-specific effects of genetic polymorphism, we performed a case-control study of the association between PD susceptibility and polymorphism of MAOB and COMT, both separately and in combination, in Taiwanese. Methods: Two hundred twenty-four patients with PD and 197 controls, matched for age, sex, and birthplace, were recruited. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. chi (2), OR, and Fisher's exact tests were used to compare differences in allelic frequencies and genotypes. Results: The MAOB G genotype (G in men and GIG in women) was associated with a 2.07-fold increased relative risk of PD. COMT polymorphism, considered alone, showed no correlation with PD risk; however, a significant synergistic enhancement was found in PD patients harboring both the COMTL and MAOB G genotypes. Conclusions: These results suggest that, in Taiwanese, PD risk is associated with MAOB G intron 13 polymorphism, and this association is augmented in the presence of the COMTL genotype, indicating an interaction of these two dopamine-metabolizing enzymes in the pathogenesis of sporadic PD. However, the relatively low frequencies of these combined genotypes in our study necessitates confirmation with a larger sample size.
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页码:375 / 382
页数:8
相关论文
共 34 条
[1]   PERMANENT HUMAN PARKINSONISM DUE TO 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) - 7 CASES [J].
BALLARD, PA ;
TETRUD, JW ;
LANGSTON, JW .
NEUROLOGY, 1985, 35 (07) :949-956
[2]   A PRIMATE MODEL OF PARKINSONISM - SELECTIVE DESTRUCTION OF DOPAMINERGIC-NEURONS IN THE PARS COMPACTA OF THE SUBSTANTIA NIGRA BY N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE [J].
BURNS, RS ;
CHIUEH, CC ;
MARKEY, SP ;
EBERT, MH ;
JACOBOWITZ, DM ;
KOPIN, IJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (14) :4546-4550
[3]   A genetic polymorphism of MAO-B modifies the association of cigarette smoking and Parkinson's disease [J].
Checkoway, H ;
Franklin, GM ;
Costa-Mallen, P ;
Smith-Weller, T ;
Dilley, J ;
Swanson, PD ;
Costa, LG .
NEUROLOGY, 1998, 50 (05) :1458-1461
[4]   Association study of NlaIII and MspI genetic polymorphisms of catechol-O-methyltransferase gene and susceptibility to schizophrenia [J].
Chen, CH ;
Lee, YR ;
Wei, FC ;
Koong, FJ ;
Hwu, HG ;
Hsiao, KJ .
BIOLOGICAL PSYCHIATRY, 1997, 41 (09) :985-987
[5]   GENETIC-MARKERS OF AN ABORIGINAL TAIWANESE POPULATION [J].
CHEN, KH ;
CANN, H ;
CHEN, TC ;
VANWEST, B ;
CAVALLISFORZA, L .
AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, 1985, 66 (03) :327-337
[6]   METABOLISM OF THE NEUROTOXIC TERTIARY AMINE, MPTP, BY BRAIN MONOAMINE-OXIDASE [J].
CHIBA, K ;
TREVOR, A ;
CASTAGNOLI, N .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (02) :574-578
[7]   SOME METHODS FOR STRENGTHENING THE COMMON X2 TESTS [J].
COCHRAN, WG .
BIOMETRICS, 1954, 10 (04) :417-451
[8]  
Costa P, 1997, AM J MED GENET, V74, P154, DOI 10.1002/(SICI)1096-8628(19970418)74:2<154::AID-AJMG7>3.3.CO
[9]  
2-A
[10]   THE OXIDANT STRESS HYPOTHESIS IN PARKINSONS-DISEASE - EVIDENCE SUPPORTING IT [J].
FAHN, S ;
COHEN, G .
ANNALS OF NEUROLOGY, 1992, 32 (06) :804-812