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  • Title: Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer's disease: geographic allele and genotype variations in Europe.
    Author: Capurso C, Solfrizzi V, D'Introno A, Colacicco AM, Capurso SA, Capurso A, Panza F.
    Journal: Exp Gerontol; 2004 Oct; 39(10):1567-73. PubMed ID: 15501028.
    Abstract:
    The interleukin 6 (IL-6) gene in humans is located in the short arm of chromosome 7 and has a-174 G/C polymorphism in its promoter region. The C allele at position-174 in the promoter of the interleukin 6 (IL-6) gene has been associated with reduced gene expression and reduced plasma levels of IL-6. Given the supposed role of several inflammatory mediators in neurodegeneration and Alzheimer's disease (AD), the IL-6-174 G/C promoter polymorphism has been associated with AD with contrasting findings. First aim of the present study was to investigate whether there was evidence in Southern Italy of an association between the IL-6-174 G/C promoter polymorphism and AD. Secondly, we also tested a possible effect of geographic genetic variations on existing reported associations comparing our results with the findings from published studies on other European populations. We examined apolipoprotein E (APOE) and IL-6-174 G/C promoter polymorphisms in a cohort of 168 sporadic AD patients and 220 sex- and age-matched nondemented controls from Southern Italy. No differences have been found in the IL-6-174 G/C promoter allele and genotype frequencies between AD patients and controls nor in early- and late-onset subsets of AD patients. No statistically significant differences in frequencies between IL-6-174 G/C promoter alleles and AD among APOE allele strata were found. Finally, comparing our results with the findings from other European populations, the IL-6*G/*G genotype frequency showed a statistically significant increasing trend from Northern to Southern regions of Europe in AD patients and controls, with a concomitant increase in IL-6*C/*G genotype frequency. Furthermore, an increasing geographical trend from North to South was found for the IL-6*G allele, with a concomitant inverse trend for IL-6*C allele. We suggest that regional European differences in genotype and allele frequencies of the IL-6-174 G/C promoter polymorphism may explain in part controversial findings on this polymorphism in AD in various European studies.
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