Affiliations: [a] Universidade do Sagrado Coração (USC), Bauru, São Paulo, Brazil | [b] Faculdade de Medicina de Marilia (FAMEMA) - Hemocentro, Marília, São Paulo, Brazil | [c] Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil | [d] Núcleo de Pesquisa em Bioquímica e Biologia Molecular da Faculdade de Medicina de São José do Rio Preto, Brazil | [e] Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, Brazil | [f] University of Cambridge, Cambridge, UK
Correspondence:
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Correspondence to: Spencer Luiz Marques Payão, Ph.D, Laboratório de Genética, Hemocentro, FAMEMA Rua Lourival Freire, 240, Bairro Fragata, CEP 17519-050, Marília, São Paulo, Brazil. Tel.: +55 14 34021856; Fax: +55 14 34330148; E-mail: [email protected].
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease that takes the form of a local overexpression of cytokines and other inflammatory molecules. We investigated three single-nucleotide polymorphisms (SNP) of the interleukin 6 gene (IL-6) promoter region [−174G/C (rs 1800795), −572C/G (rs 1800796), and −597G/A (rs 1800797)] in 200 patients with late-onset AD and 165 elderly controls in a Brazilian case-control population sample. Genotyping was carried out from blood cells using PCR-RFLP techniques. Statistical analysis was performed to evaluate the Hardy-Weinberg equilibrium and to compare frequencies between groups. No association was found between any IL-6 polymorphism and AD; however the haplotype composed of the −597 A allele and the −174G allele indicated a crude odds ratio (OR) of 0.15 (p = 0.0021) and a significantly adjusted OR (adjusted for the APOE E4 allele value) of 0.15 (p = 0.00294). Linkage disequilibrium was D' = 0.68 among the three SNPs. Our findings revealed a protective effect of AG (−597A, −174G) haplotype, which worked independently of the APOE E4 allele in our Brazilian population sample. Thus, the promoter region of IL-6 gene probably exerts an effect through gene linkage and/or gene interaction.
Keywords: Association study, case-control study, haplotype, interleukin 6 gene, polymorphisms
