Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain

被引:150
作者
Licastro, F
Grimaldi, LME
Bonafè, M
Martina, C
Olivieri, F
Cavallone, L
Giovanietti, S
Masliah, E
Franceschi, C
机构
[1] Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy
[2] Dept Neurosci, Caltanisetta, Italy
[3] INRCA Res Dept, Ancona, Italy
[4] Univ Calif San Diego, Dept Neurosci & Pathol, San Diego, CA 92103 USA
关键词
Alzheimer's disease risk; IL-6; gene; blood and brain IL-6 levels;
D O I
10.1016/S0197-4580(03)00013-7
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Two different polymorphic regions of the interleukin-6 (IL-6) gene were investigated in patients with Alzheimer's disease (AD) and non-demented controls. The - 174 C allele in the promoter region of IL-6 gene was over-represented in AD patients compared to controls and significantly increased the risk of AD. Moreover, the - 174 CC genotype was associated with a high risk of the disease in women. The D allele of a variable number of tandem repeat (VNTR) was in strong linkage disequilibrium with the - 174 C allele and slightly increased AD risk. On the other hand, the frequency of the VNTR C allele was decreased in patients with AD and was negatively associated with the risk of developing AD. Both the - 174 CC and VNTR DD genotypes were also associated with increased IL-6 levels in the blood and brain from AD. These findings suggest that IL-6 may play a multifaceted role in AD by affecting the turnover of the cytokine. (C) 2003 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:921 / 926
页数:6
相关论文
共 39 条
[1]   Serum interleukin-6 and interleukin-6 soluble receptor in Alzheimer's disease [J].
Angelis, P ;
Scharf, S ;
Mander, A ;
Vajda, F ;
Christophidis, N .
NEUROSCIENCE LETTERS, 1998, 244 (02) :106-108
[2]   Association between an interleukin-6 promoter and 3′ flanking region haplotype and reduced Alzheimer's disease risk in a German population [J].
Bagli, M ;
Papassotiropoulos, A ;
Knapp, M ;
Jessen, F ;
Rao, ML ;
Maier, W ;
Heun, R .
NEUROSCIENCE LETTERS, 2000, 283 (02) :109-112
[3]   INTERLEUKIN-6 AND ALPHA-2-MACROGLOBULIN INDICATE AN ACUTE-PHASE STATE IN ALZHEIMERS-DISEASE CORTICES [J].
BAUER, J ;
STRAUSS, S ;
SCHREITERGASSER, U ;
GANTER, U ;
SCHLEGEL, P ;
WITT, I ;
YOLK, B ;
BERGER, M .
FEBS LETTERS, 1991, 285 (01) :111-114
[4]   PATTERNS OF GLIOSIS IN ALZHEIMERS-DISEASE AND AGING CEREBRUM [J].
BEACH, TG ;
WALKER, R ;
MCGEER, EG .
GLIA, 1989, 2 (06) :420-436
[5]   Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer's disease [J].
Bhojak, TJ ;
DeKosky, ST ;
Ganguli, M ;
Kamboh, MI .
NEUROSCIENCE LETTERS, 2000, 288 (01) :21-24
[6]   RAPID DETECTION AND SEQUENCING OF ALLELES IN THE 3' FLANKING REGION OF THE INTERLEUKIN-6 GENE [J].
BOWCOCK, AM ;
RAY, A ;
ERLICH, H ;
SEHGAL, PB .
NUCLEIC ACIDS RESEARCH, 1989, 17 (17) :6855-6864
[7]   INVERSE ASSOCIATION OF ANTIINFLAMMATORY TREATMENTS AND ALZHEIMERS-DISEASE - INITIAL RESULTS OF A COTWIN CONTROL STUDY [J].
BREITNER, JCS ;
GAU, BA ;
WELSH, KA ;
PLASSMAN, BL ;
MCDONALD, WM ;
HELMS, MJ ;
ANTHONY, JC .
NEUROLOGY, 1994, 44 (02) :227-232
[8]   NEUROLOGIC DISEASE INDUCED IN TRANSGENIC MICE BY CEREBRAL OVEREXPRESSION OF INTERLEUKIN-6 [J].
CAMPBELL, IL ;
ABRAHAM, CR ;
MASLIAH, E ;
KEMPER, P ;
INGLIS, JD ;
OLDSTONE, MBA ;
MUCKE, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :10061-10065
[9]   GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].
CORDER, EH ;
SAUNDERS, AM ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
SCIENCE, 1993, 261 (5123) :921-923
[10]   INTERLEUKIN-6 - A CYTOKINE FOR GERONTOLOGISTS [J].
ERSHLER, WB .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 1993, 41 (02) :176-181