Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10 gene polymorphisms to susceptibility to Mediterranean spotted fever.
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.
Forte
Giusi Irma
GI
Clinical Pathology, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Palermo, Italy.
Scola
Letizia
L
Misiano
Gabriella
G
Milano
Salvatore
S
Mansueto
Pasquale
P
Vitale
Giustina
G
Bellanca
Fiamma
F
Sanacore
Maria
M
Vaccarino
Loredana
L
Rini
Giovan Battista
GB
Caruso
Calogero
C
Cillari
Enrico
E
Lio
Domenico
D
Mansueto
Serafino
S
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*
C508609:IL10 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma