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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. 2009

P Vural, and S Değirmencioğlu, and H Parildar-Karpuzoğlu, and S Doğru-Abbasoğlu, and H A Hanagasi, and B Karadağ, and H Gürvit, and M Emre, and M Uysal
Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, 34093, Istanbul, Turkey. pervinvural@yahoo.com

OBJECTIVE Single nucleotide polymorphisms in the regulatory regions of the cytokine genes for tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6 and IL-10 have been suggested to influence the risk of Alzheimer's disease (AD) with conflicting results. OBJECTIVE To investigate the TNFalpha-308, IL-6 -174 and IL-10 -1082 gene polymorphisms as susceptibility factors for AD. METHODS We analyzed genotype and allele distributions of these polymorphisms in 101 sporadic AD patients and 138 healthy controls. RESULTS Heterozygotes (AG) or combined genotype (AG+AA) for IL-10 -1082 were associated with approximately two-fold increase in the risk of AD. Carriers of A alleles of both TNFalpha-308 and IL-10 -1082 had 6.5 times higher risk for AD in comparison with non-carriers. Concomitant presence of both mutant TNFalpha-308 A and IL-6 -174 C alleles raised three-fold the AD risk, whereas there was no notable risk for AD afflicted by IL-6 -174 polymorphism alone. CONCLUSIONS Our results suggest that TNFalpha and IL-10 promoter polymorphism might be a risk factor for AD. The combined effects of TNFalpha-308, IL-6 -174 and IL-10 -1082 variant alleles may be more decisive to induce functional differences and modify the risk for AD.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D003430 Cross-Sectional Studies Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time. Disease Frequency Surveys,Prevalence Studies,Analysis, Cross-Sectional,Cross Sectional Analysis,Cross-Sectional Survey,Surveys, Disease Frequency,Analyses, Cross Sectional,Analyses, Cross-Sectional,Analysis, Cross Sectional,Cross Sectional Analyses,Cross Sectional Studies,Cross Sectional Survey,Cross-Sectional Analyses,Cross-Sectional Analysis,Cross-Sectional Study,Cross-Sectional Surveys,Disease Frequency Survey,Prevalence Study,Studies, Cross-Sectional,Studies, Prevalence,Study, Cross-Sectional,Study, Prevalence,Survey, Cross-Sectional,Survey, Disease Frequency,Surveys, Cross-Sectional
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha

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