title: Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease.
abstract: BACKGROUND
  Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10).
  
  
  METHODS
  We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls.
  
  
  RESULTS
  We replicated the interaction. For IL6 rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded.
  
  
  CONCLUSIONS
  We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD.
authors.affiliation: Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital (University of Cantabria), 39008 Santander, Spain. combarro@unican.es
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Naomi
authors.initials: N
authors.lastname: Hammond
authors.forename: Olivia
authors.initials: O
authors.lastname: Belbin
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arias-Vásquez
authors.forename: Mario
authors.initials: M
authors.lastname: Cortina-Borja
authors.forename: Michael G
authors.initials: MG
authors.lastname: Lehmann
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Maaike
authors.initials: M
authors.lastname: Schuur
authors.forename: Heike
authors.initials: H
authors.lastname: Kölsch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Heun
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Wilcock
authors.forename: Kristelle
authors.initials: K
authors.lastname: Brown
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.forename: Rachel
authors.initials: R
authors.lastname: Harrison
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mateo
authors.forename: Rhian
authors.initials: R
authors.lastname: Gwilliam
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.forename: Donald R
authors.initials: DR
authors.lastname: Warden
authors.forename: A David
authors.initials: AD
authors.lastname: Smith
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Lehmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics / Q000276:immunology; D004252:DNA Mutational Analysis; D004660:Encephalitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D015850:Interleukin-6; D016753:Interleukin-10
references.citation: Immunol Lett. 2008 May 15;117(2):198-202
references.pmid: 18367253
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Crit Rev Immunol. 2001;21(5):427-49
references.pmid: 11942558
references.citation: Twin Res Hum Genet. 2005 Apr;8(2):132-7
references.pmid: 15901476
references.citation: Rheumatology (Oxford). 2000 Nov;39(11):1180-8
references.pmid: 11085795
references.citation: Transplantation. 2003 Mar 15;75(5):711-7
references.pmid: 12640314
references.citation: Am J Cardiol. 2003 Sep 1;92(5):522-8
references.pmid: 12943870
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: Am J Med. 2003 Feb 15;114(3):180-7
references.pmid: 12637131
references.citation: Neurobiol Aging. 2000 May-Jun;21(3):383-421
references.pmid: 10858586
references.citation: Stroke. 1995 Aug;26(8):1393-8
references.pmid: 7631343
references.citation: Neurology. 1991 Apr;41(4):479-86
references.pmid: 2011243
references.citation: Circulation. 2003 Nov 11;108(19):2317-22
references.pmid: 14568895
references.citation: Neurobiol Aging. 2007 Dec;28(12):1810-20
references.pmid: 17011077
references.citation: Neurobiol Aging. 1994 Nov-Dec;15(6):771-2
references.pmid: 7534383
references.citation: Neurology. 2002 Aug 13;59(3):371-8
references.pmid: 12177370
references.citation: Eur J Immunogenet. 1997 Feb;24(1):1-8
references.pmid: 9043871
references.citation: Cytokine. 2005 May 21;30(4):188-94
references.pmid: 15863393
references.citation: Arch Neurol. 2000 Aug;57(8):1153-60
references.pmid: 10927795
references.citation: Brain Res. 1993 Dec 3;629(2):245-52
references.pmid: 7509248
references.citation: J Biol Chem. 2000 Jun 16;275(24):18138-44
references.pmid: 10747905
references.citation: Neuro Endocrinol Lett. 2008 Feb;29(1):75-9
references.pmid: 18283248
references.citation: Neurosci Lett. 1990 Jan 22;108(3):350-4
references.pmid: 2304653
references.citation: Arch Neurol. 2009 Mar;66(3):300-5
references.pmid: 19273747
references.citation: FEBS Lett. 1991 Jul 8;285(1):111-4
references.pmid: 1712317
references.citation: Eur Arch Psychiatry Clin Neurosci. 2005 Aug;255(4):269-78
references.pmid: 15565298
references.citation: Gut. 2004 Aug;53(8):1082-9
references.pmid: 15247172
references.citation: Science. 2002 Jul 19;297(5580):353-6
references.pmid: 12130773
references.citation: BMC Res Notes. 2009 Jun 15;2:105
references.pmid: 19527493
references.citation: Circulation. 2000 Apr 18;101(15):1767-72
references.pmid: 10769275
references.citation: J Am Geriatr Soc. 1993 Feb;41(2):176-81
references.pmid: 8426042
references.citation: Cell Mol Life Sci. 2002 Mar;59(3):560-9
references.pmid: 11964134
references.citation: Genetica. 2001;112-113:59-69
references.pmid: 11838787
references.citation: Neurology. 2003 Jul 8;61(1):76-80
references.pmid: 12847160
references.citation: J Am Geriatr Soc. 2002 Apr;50(4):638-44
references.pmid: 11982663
references.citation: Brain Res Mol Brain Res. 2000 Apr 14;77(1):138-47
references.pmid: 10814840
references.citation: N Engl J Med. 2009 Apr 23;360(17):1718-28
references.pmid: 19369658
references.citation: Neurobiol Aging. 1996 Sep-Oct;17(5):681-6
references.pmid: 8892340
references.citation: Genes Immun. 2000 Feb;1(3):185-90
references.pmid: 11196710
references.citation: Arch Gen Psychiatry. 1997 Mar;54(3):264-70
references.pmid: 9075467
references.citation: Mol Neurobiol. 1997 Dec;15(3):307-39
references.pmid: 9457704
references.citation: Am J Med. 1999 May;106(5):506-12
references.pmid: 10335721
references.citation: Free Radic Biol Med. 2002 Dec 1;33(11):1475-9
references.pmid: 12446204
references.citation: Bioessays. 2005 Jun;27(6):637-46
references.pmid: 15892116
references.citation: J Neuroimmunol. 2000 Feb 1;103(1):97-102
references.pmid: 10674995
references.citation: Food Nutr Bull. 2008 Jun;29(2 Suppl):S143-72
references.pmid: 18709889
references.citation: Neurobiol Aging. 2009 Sep;30(9):1333-49
references.pmid: 18206267
references.citation: Neurochem Int. 2007 Jan;50(1):12-38
references.pmid: 16973241
references.citation: Clin Exp Immunol. 1999 Sep;117(3):476-81
references.pmid: 10469050
references.citation: Liver Transpl. 2003 Feb;9(2):170-81
references.pmid: 12548511
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):9090-5
references.pmid: 12840146
references.citation: J Neuroimmunol. 2001 Feb 1;113(1):49-62
references.pmid: 11137576
references.citation: Neurology. 2005 Apr 26;64(8):1371-7
references.pmid: 15851726
references.citation: Genes Immun. 2002 Nov;3(7):407-13
references.pmid: 12424622
references.citation: Stroke. 2002 Apr;33(4):982-7
references.pmid: 11935048
references.citation: J Neurochem. 1999 Apr;72(4):1466-71
references.pmid: 10098850
references.citation: Circulation. 2001 Feb 20;103(7):947-53
references.pmid: 11181468
references.citation: Arthritis Rheum. 1999 Jun;42(6):1101-8
references.pmid: 10366102
references.citation: Nat Genet. 2007 Jan;39(1):17-23
references.pmid: 17192785
references.citation: Diabetes Res Clin Pract. 2006 Mar;71(3):299-305
references.pmid: 16140413
references.citation: Arch Neurol. 2004 May;61(5):668-72
references.pmid: 15148142
references.citation: Alzheimer Dis Assoc Disord. 1998 Sep;12(3):215-27
references.pmid: 9772027
references.citation: J Clin Invest. 1998 Oct 1;102(7):1369-76
references.pmid: 9769329
references.citation: JAMA. 2001 Jul 18;286(3):327-34
references.pmid: 11466099
references.citation: Neurology. 2004 Sep 28;63(6):1135-6
references.pmid: 15452323