title: Polymorphisms in cytokine genes IL6, TNF, IL10, IL17A and IFNG influence susceptibility to complicated skin and skin structure infections.
abstract: Complicated skin and skin structure infections (cSSSIs) are caused by Gram-positive and Gram-negative, aerobic and anaerobic pathogens, with a polymicrobial aetiology being frequent. Recognition of invading pathogens by the immune system results in the production of pro- and anti-inflammatory cytokines, which are extremely important for intercellular communication and control of infection. This study assessed whether genetic variation in genes encoding cytokines influences the susceptibility to cSSSIs. For the association study, 318 patients with cSSSI and 328 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) in cytokine genes IL1A, IL1B, IL1RN, TNF, IL10, IL17A, IL17F and IFNG. For immunological validation, peripheral blood mononuclear cells (PBMCs) from 74 healthy individuals, genotyped for SNPs of interest, were stimulated with Staphylococcus aureus or Escherichia coli and corresponding cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). Polymorphisms IL6 rs1800797, TNF rs1800629, IL10 rs1800871, IL17A rs8193036 and IFNG rs2069705 influenced susceptibility to cSSSIs. No differences in cytokine responses, stratified for genotype, were detected after PBMC stimulation. No association with cSSSIs was observed for polymorphisms IL1A rs17561 and rs1800587, IL1B rs16944 and rs1143627, IL1RN rs4251961, TNF rs361525, IL10 rs1800896, IL17A rs2275913 and IL17F rs763780. In conclusion, polymorphisms in IL6, TNF, IL10, IL17A and IFNG are associated with susceptibility to cSSSIs.
authors.affiliation: Department of Internal Medicine (463), Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: M H T
authors.initials: MH
authors.lastname: Stappers
authors.forename: Y
authors.initials: Y
authors.lastname: Thys
authors.forename: M
authors.initials: M
authors.lastname: Oosting
authors.forename: T S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: M
authors.initials: M
authors.lastname: Ioana
authors.forename: P
authors.initials: P
authors.lastname: Reimnitz
authors.forename: J W
authors.initials: JW
authors.lastname: Mouton
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: L A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: I C
authors.initials: IC
authors.lastname: Gyssens
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017192:Skin Diseases, Bacterial / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines