title: Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10 gene polymorphisms to susceptibility to Mediterranean spotted fever.
abstract: The acute phase of Mediterranean spotted fever (MSF) is characterized by dramatic changes in cytokine production patterns, clearly indicating their role in the immunomodulation of the response against the microorganism, and the differences in cytokine production seem to influence the extent and severity of the disease. In this study, the single nucleotide polymorphisms (SNPs) of tumor necrosis factor alpha (TNF-alpha) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma interferon (IFN-gamma) T/A SNP at position +874 (rs2430561) were typed in 80 Sicilian patients affected by MSF and in 288 control subjects matched for age, gender, and geographic origin. No significant differences in TNF-alpha -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-gamma, was found to be significantly less frequent in MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence interval [95% CI], 0.06 to 0.51; P corrected for the number of genotypes [Pc], 0.0021). In addition, when evaluating the IFN-gamma and IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; P(c), 0.0027) combined genotypes was observed. In conclusion, our data strongly suggest that finely genetically tuned cytokine production may play a crucial role in the regulation of the immune response against rickettsial infection, therefore influencing the disease outcomes, ranging from nonapparent or subclinical condition to overt or fatal disease.
authors.affiliation: Clinical Pathology, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Palermo, Italy.
authors.forename: Giusi Irma
authors.initials: GI
authors.lastname: Forte
authors.forename: Letizia
authors.initials: L
authors.lastname: Scola
authors.forename: Gabriella
authors.initials: G
authors.lastname: Misiano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Milano
authors.forename: Pasquale
authors.initials: P
authors.lastname: Mansueto
authors.forename: Giustina
authors.initials: G
authors.lastname: Vitale
authors.forename: Fiamma
authors.initials: F
authors.lastname: Bellanca
authors.forename: Maria
authors.initials: M
authors.lastname: Sanacore
authors.forename: Loredana
authors.initials: L
authors.lastname: Vaccarino
authors.forename: Giovan Battista
authors.initials: GB
authors.lastname: Rini
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
authors.forename: Enrico
authors.initials: E
authors.lastname: Cillari
authors.forename: Domenico
authors.initials: D
authors.lastname: Lio
authors.forename: Serafino
authors.initials: S
authors.lastname: Mansueto
mesh_terms: D000328:Adult; D001907:Boutonneuse Fever / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012802:Sicily; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C508609:IL10 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma