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Erschienen in: Journal of Neurology 3/2012

01.03.2012 | Review

Association between polymorphism in the promoter region of Interleukin 6 (-174 G/C) and risk of Alzheimer’s disease: a meta-analysis

verfasst von: Limeng Dai, Dan Liu, Hong Guo, Yanyan Wang, Yun Bai

Erschienen in: Journal of Neurology | Ausgabe 3/2012

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Abstract

Studies of the relationship between Alzheimer’s disease (AD) and polymorphism in the promoter region of Interleukin 6 (IL-6) -174 G/C have reported inconsistent results. To assess the association between IL-6 -174 G/C promoter polymorphism and AD risk, a meta-analysis containing 3,101 AD cases and 3,860 controls from 18 case–control studies was performed. There were 16 studies involving Europeans and 2 studies involving non-Europeans. The combined results showed significant differences in recessive model [CC versus GC + GG, odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.54–0.90] and heterozygote comparison (CC versus GC, OR = 0.76, 95% CI = 0.60–0.96) on the basis of all studies. On subgroup analysis by ethnicity, similarly significant differences in recessive model (CC versus GC + GG) were found in both Europeans and non-Europeans, but significant difference in heterozygote comparison (CC versus GC) was found only in non-Europeans. In conclusion, there were statistically significant differences in genotype distribution of IL-6 -174 G/C between AD cases and controls in recessive model (CC versus GC + GG). Genotype CC of IL-6 -174 G/C could decrease the risk of AD. Further studies with large sample size, especially in subgroup analysis, should be done.
Literatur
1.
Zurück zum Zitat Arosio B, Trabattoni D, Galimberti L, Bucciarelli P, Fasano F, Calabresi C, Cazzullo CL, Vergani C, Annoni G, Clerici M (2004) Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer’s disease. Neurobiol Aging 25:1009–1015PubMedCrossRef Arosio B, Trabattoni D, Galimberti L, Bucciarelli P, Fasano F, Calabresi C, Cazzullo CL, Vergani C, Annoni G, Clerici M (2004) Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer’s disease. Neurobiol Aging 25:1009–1015PubMedCrossRef
2.
Zurück zum Zitat Bagli M, Papassotiropoulos A, Knapp M, Jessen F, Luise Rao M, Maier W, Heun R (2000) Association between an interleukin-6 promoter and 3′ flanking region haplotype and reduced Alzheimer’s disease risk in a German population. Neurosci Lett 283:109–112PubMedCrossRef Bagli M, Papassotiropoulos A, Knapp M, Jessen F, Luise Rao M, Maier W, Heun R (2000) Association between an interleukin-6 promoter and 3′ flanking region haplotype and reduced Alzheimer’s disease risk in a German population. Neurosci Lett 283:109–112PubMedCrossRef
3.
Zurück zum Zitat Bhojak TJ, DeKosky ST, Ganguli M, Kamboh MI (2000) Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer’s disease. Neurosci Lett 288:21–24PubMedCrossRef Bhojak TJ, DeKosky ST, Ganguli M, Kamboh MI (2000) Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer’s disease. Neurosci Lett 288:21–24PubMedCrossRef
4.
Zurück zum Zitat Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191PubMedCrossRef Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191PubMedCrossRef
5.
Zurück zum Zitat Campbell IL, Stalder AK, Chiang CS, Bellinger R, Heyser CJ, Steffensen S, Masliah E, Powell HC, Gold LH, Henriksen SJ, Siggins GR (1997) Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 2:125–129PubMedCrossRef Campbell IL, Stalder AK, Chiang CS, Bellinger R, Heyser CJ, Steffensen S, Masliah E, Powell HC, Gold LH, Henriksen SJ, Siggins GR (1997) Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry 2:125–129PubMedCrossRef
6.
Zurück zum Zitat Capurso C, Solfrizzi V, Colacicco AM, D’Introno A, Frisardi V, Imbimbo BP, Lorusso M, Vendemiale G, Denitto M, Santamato A, Seripa D, Pilotto A, Fiore P, Capurso A, Panza F (2010) Interleukin 6-174 G/C promoter and variable number of tandem repeats (VNTR) gene polymorphisms in sporadic Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 34:177–182PubMedCrossRef Capurso C, Solfrizzi V, Colacicco AM, D’Introno A, Frisardi V, Imbimbo BP, Lorusso M, Vendemiale G, Denitto M, Santamato A, Seripa D, Pilotto A, Fiore P, Capurso A, Panza F (2010) Interleukin 6-174 G/C promoter and variable number of tandem repeats (VNTR) gene polymorphisms in sporadic Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 34:177–182PubMedCrossRef
7.
Zurück zum Zitat Capurso C, Solfrizzi V, D’Introno A, Colacicco AM, Capurso SA, Capurso A, Panza F (2004) Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer’s disease: geographic allele and genotype variations in Europe. Exp Gerontol 39:1567–1573PubMedCrossRef Capurso C, Solfrizzi V, D’Introno A, Colacicco AM, Capurso SA, Capurso A, Panza F (2004) Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer’s disease: geographic allele and genotype variations in Europe. Exp Gerontol 39:1567–1573PubMedCrossRef
8.
Zurück zum Zitat Combarros O, Infante J, Llorca J, Pena N, Fernandez-Viadero C, Berciano J (2005) Interaction between interleukin-6 and intercellular adhesion molecule-1 genes and Alzheimer’s disease risk. J Neurol 252:485–487PubMedCrossRef Combarros O, Infante J, Llorca J, Pena N, Fernandez-Viadero C, Berciano J (2005) Interaction between interleukin-6 and intercellular adhesion molecule-1 genes and Alzheimer’s disease risk. J Neurol 252:485–487PubMedCrossRef
9.
Zurück zum Zitat Depboylu C, Lohmuller F, Gocke P, Du Y, Zimmer R, Gasser T, Klockgether T, Dodel RC (2004) An interleukin-6 promoter variant is not associated with an increased risk for Alzheimer’s disease. Dement Geriatr Cogn Disord 17:170–173PubMedCrossRef Depboylu C, Lohmuller F, Gocke P, Du Y, Zimmer R, Gasser T, Klockgether T, Dodel RC (2004) An interleukin-6 promoter variant is not associated with an increased risk for Alzheimer’s disease. Dement Geriatr Cogn Disord 17:170–173PubMedCrossRef
10.
Zurück zum Zitat Faltraco F, Burger K, Zill P, Teipel SJ, Moller HJ, Hampel H, Bondy B, Ackenheil M (2003) Interleukin-6-174 G/C promoter gene polymorphism C allele reduces Alzheimer’s disease risk. J Am Geriatr Soc 51:578–579PubMedCrossRef Faltraco F, Burger K, Zill P, Teipel SJ, Moller HJ, Hampel H, Bondy B, Ackenheil M (2003) Interleukin-6-174 G/C promoter gene polymorphism C allele reduces Alzheimer’s disease risk. J Am Geriatr Soc 51:578–579PubMedCrossRef
11.
Zurück zum Zitat Fontalba A, Gutierrez O, Llorca J, Mateo I, Vazquez-Higuera JL, Berciano J, Fernandez-Luna JL, Combarros O (2009) Gene–gene interaction between CARD8 and interleukin-6 reduces Alzheimer’s disease risk. J Neurol 256:1184–1186PubMedCrossRef Fontalba A, Gutierrez O, Llorca J, Mateo I, Vazquez-Higuera JL, Berciano J, Fernandez-Luna JL, Combarros O (2009) Gene–gene interaction between CARD8 and interleukin-6 reduces Alzheimer’s disease risk. J Neurol 256:1184–1186PubMedCrossRef
12.
Zurück zum Zitat Infante J, Sanz C, Fernandez-Luna JL, Llorca J, Berciano J, Combarros O (2004) Gene–gene interaction between interleukin-6 and interleukin-10 reduces AD risk. Neurology 63:1135–1136PubMed Infante J, Sanz C, Fernandez-Luna JL, Llorca J, Berciano J, Combarros O (2004) Gene–gene interaction between interleukin-6 and interleukin-10 reduces AD risk. Neurology 63:1135–1136PubMed
13.
Zurück zum Zitat Klimkowicz-Mrowiec A, Wolkow P, Spisak K, Maruszak A, Styczynska M, Barcikowska M, Szczudlik A, Slowik A (2010) Interleukin-6 gene–174 C/G and apolipoprotein E gene polymorphisms and the risk of Alzheimer disease in a Polish population. Neurol Neurochir Pol 44:537–541PubMed Klimkowicz-Mrowiec A, Wolkow P, Spisak K, Maruszak A, Styczynska M, Barcikowska M, Szczudlik A, Slowik A (2010) Interleukin-6 gene–174 C/G and apolipoprotein E gene polymorphisms and the risk of Alzheimer disease in a Polish population. Neurol Neurochir Pol 44:537–541PubMed
14.
Zurück zum Zitat Koivisto AM, Helisalmi S, Pihlajamaki J, Moilanen L, Kuusisto J, Laakso M, Hiltunen M, Keijo K, Hanninen T, Helkala EL, Kervinen K, Kesaniemi YA, Soininen H (2005) Interleukin-6 promoter polymorphism and late-onset Alzheimer’s disease in the Finnish population. J Neurogenet 19:155–161PubMedCrossRef Koivisto AM, Helisalmi S, Pihlajamaki J, Moilanen L, Kuusisto J, Laakso M, Hiltunen M, Keijo K, Hanninen T, Helkala EL, Kervinen K, Kesaniemi YA, Soininen H (2005) Interleukin-6 promoter polymorphism and late-onset Alzheimer’s disease in the Finnish population. J Neurogenet 19:155–161PubMedCrossRef
15.
Zurück zum Zitat Licastro F, Grimaldi LM, Bonafe M, Martina C, Olivieri F, Cavallone L, Giovanietti S, Masliah E, Franceschi C (2003) Interleukin-6 gene alleles affect the risk of Alzheimer’s disease and levels of the cytokine in blood and brain. Neurobiol Aging 24:921–926PubMedCrossRef Licastro F, Grimaldi LM, Bonafe M, Martina C, Olivieri F, Cavallone L, Giovanietti S, Masliah E, Franceschi C (2003) Interleukin-6 gene alleles affect the risk of Alzheimer’s disease and levels of the cytokine in blood and brain. Neurobiol Aging 24:921–926PubMedCrossRef
16.
Zurück zum Zitat Mansoori N, Tripathi M, Alam R, Luthra K, Ramakrishnan L, Parveen S, Mukhopadhyay AK (2010) IL-6-174 G/C and ApoE gene polymorphisms in Alzheimer’s and vascular dementia patients attending the cognitive disorder clinic of the All India Institute of Medical Sciences, New Delhi. Dement Geriatr Cogn Disord 30:461–468PubMedCrossRef Mansoori N, Tripathi M, Alam R, Luthra K, Ramakrishnan L, Parveen S, Mukhopadhyay AK (2010) IL-6-174 G/C and ApoE gene polymorphisms in Alzheimer’s and vascular dementia patients attending the cognitive disorder clinic of the All India Institute of Medical Sciences, New Delhi. Dement Geriatr Cogn Disord 30:461–468PubMedCrossRef
17.
Zurück zum Zitat Papassotiropoulos A, Hock C, Nitsch RM (2001) Genetics of interleukin 6: implications for Alzheimer’s disease. Neurobio Aging 22:863–871CrossRef Papassotiropoulos A, Hock C, Nitsch RM (2001) Genetics of interleukin 6: implications for Alzheimer’s disease. Neurobio Aging 22:863–871CrossRef
18.
Zurück zum Zitat Paradowski B, Celczynska D, Dodosz T, Noga L (2008) Polymorphism 174 G/C of interleukin 6 gene in Alzheimer’s disease—preliminary report. Neurol Neurochir Pol 42:312–315PubMed Paradowski B, Celczynska D, Dodosz T, Noga L (2008) Polymorphism 174 G/C of interleukin 6 gene in Alzheimer’s disease—preliminary report. Neurol Neurochir Pol 42:312–315PubMed
19.
Zurück zum Zitat Pola R, Flex A, Gaetani E, Lago AD, Gerardino L, Pola P, Bernabei R (2002) The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with Alzheimer’s disease in an Italian population. Neuroreport 13:1645–1647PubMedCrossRef Pola R, Flex A, Gaetani E, Lago AD, Gerardino L, Pola P, Bernabei R (2002) The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with Alzheimer’s disease in an Italian population. Neuroreport 13:1645–1647PubMedCrossRef
20.
Zurück zum Zitat Ribizzi G, Fiordoro S, Barocci S, Ferrari E, Megna M (2010) Cytokine polymorphisms and Alzheimer disease: possible associations. Neurol Sci 31:321–325PubMedCrossRef Ribizzi G, Fiordoro S, Barocci S, Ferrari E, Megna M (2010) Cytokine polymorphisms and Alzheimer disease: possible associations. Neurol Sci 31:321–325PubMedCrossRef
21.
Zurück zum Zitat Shawkatova I, Javor J, Parnicka Z, Vrazda L, Novak M, Buc M (2010) No association between cytokine gene polymorphism and risk of Alzheimer’s disease in Slovaks. Acta Neurobiol Exp 70:303–307 Shawkatova I, Javor J, Parnicka Z, Vrazda L, Novak M, Buc M (2010) No association between cytokine gene polymorphism and risk of Alzheimer’s disease in Slovaks. Acta Neurobiol Exp 70:303–307
22.
Zurück zum Zitat Shibata N, Ohnuma T, Takahashi T, Baba H, Ishizuka T, Ohtsuka M, Ueki A, Nagao M, Arai H (2002) Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype–phenotype association study in Japanese cases. Am J Med Genet 114:436–439PubMedCrossRef Shibata N, Ohnuma T, Takahashi T, Baba H, Ishizuka T, Ohtsuka M, Ueki A, Nagao M, Arai H (2002) Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype–phenotype association study in Japanese cases. Am J Med Genet 114:436–439PubMedCrossRef
23.
Zurück zum Zitat van Oijen M, Arp PP, de Jong FJ, Hofman A, Koudstaal PJ, Uitterlinden AG, Breteler MM (2006) Polymorphisms in the interleukin 6 and transforming growth factor beta1 gene and risk of dementia. The Rotterdam Study. Neurosci Lett 402:113–117PubMedCrossRef van Oijen M, Arp PP, de Jong FJ, Hofman A, Koudstaal PJ, Uitterlinden AG, Breteler MM (2006) Polymorphisms in the interleukin 6 and transforming growth factor beta1 gene and risk of dementia. The Rotterdam Study. Neurosci Lett 402:113–117PubMedCrossRef
24.
Zurück zum Zitat Vural P, Degirmencioglu S, Parildar-Karpuzoglu H, Dogru-Abbasoglu S, Hanagasi HA, Karadag B, Gurvit H, Emre M, Uysal M (2009) The combinations of TNFalpha-308 and IL-6-174 or IL-10-1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer’s disease. Acta Neurol Scand 120:396–401PubMedCrossRef Vural P, Degirmencioglu S, Parildar-Karpuzoglu H, Dogru-Abbasoglu S, Hanagasi HA, Karadag B, Gurvit H, Emre M, Uysal M (2009) The combinations of TNFalpha-308 and IL-6-174 or IL-10-1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer’s disease. Acta Neurol Scand 120:396–401PubMedCrossRef
25.
Zurück zum Zitat Wilson CJ, Finch CE, Cohen HJ (2002) Cytokines and cognition–the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc 50:2041–2056PubMedCrossRef Wilson CJ, Finch CE, Cohen HJ (2002) Cytokines and cognition–the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc 50:2041–2056PubMedCrossRef
26.
Zurück zum Zitat Zhang Y, Hayes A, Pritchard A, Thaker U, Haque MS, Lemmon H, Harris J, Cumming A, Lambert JC, Chartier-Harlin MC, St Clair D, Iwatsubo T, Mann DM, Lendon CL (2004) Interleukin-6 promoter polymorphism: risk and pathology of Alzheimer’s disease. Neurosci Lett 362:99–102PubMedCrossRef Zhang Y, Hayes A, Pritchard A, Thaker U, Haque MS, Lemmon H, Harris J, Cumming A, Lambert JC, Chartier-Harlin MC, St Clair D, Iwatsubo T, Mann DM, Lendon CL (2004) Interleukin-6 promoter polymorphism: risk and pathology of Alzheimer’s disease. Neurosci Lett 362:99–102PubMedCrossRef
Metadaten
Titel
Association between polymorphism in the promoter region of Interleukin 6 (-174 G/C) and risk of Alzheimer’s disease: a meta-analysis
verfasst von
Limeng Dai
Dan Liu
Hong Guo
Yanyan Wang
Yun Bai
Publikationsdatum
01.03.2012
Verlag
Springer-Verlag
Erschienen in
Journal of Neurology / Ausgabe 3/2012
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-011-6164-0

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