PMID- 22922140 OWN - NLM STAT- MEDLINE DCOM- 20130502 LR - 20220317 IS - 1732-2693 (Electronic) IS - 0032-5449 (Linking) VI - 66 DP - 2012 Jun 20 TI - The impact of IL18 gene polymorphisms on mRNA levels and interleukin-18 release by peripheral blood mononuclear cells. PG - 409-14 AB - INTRODUCTION: Interleukin-18 (IL-18) is a pleiotropic cytokine playing an important role as a modulator of immune responses, found to play a role in pathogenesis of numerous inflammatory-associated disorders. In the present study a potential association between 7 common single-nucleotide polymorphisms (SNPs) spanning the whole IL18 gene, gene expression and the release of IL-18 from the stimulated peripheral blood mononuclear cells (PBMCs) was investigated. MATERIALS/METHODS: PBMCs were isolated from peripheral blood of 29 healthy volunteers, genotyped for the presence of IL18 SNPs: rs1946518: A>C, rs187238: G>C, rs360718: A>C, rs360722: C>T, rs360721: C>G, rs549908: T>G, and rs5744292: A>G. IL-18 concentration and IL18 mRNA levels were investigated after incubation of cells for 48 h with different stimulants (PHA, LPS, and anti-CD3/CD28 antibodies). RESULTS: After treatment with LPS and antibodies IL-18 concentrations were significantly lower in rs1946518AA homozygotes than in C allele carriers. When differences in IL18 mRNA levels between non-stimulated and stimulated cells were analyzed, significantly decreased gene expression was noted in rs1946518 AA homozygotes (as compared with C allele carriers) in samples treated with PHA and LPS. Similar trends were observed in the case of rs187238 SNP; however, the differences reached statistical significance only after PHA treatment. CONCLUSIONS: Our study supports the role of rs1946518 (-607A>C) and rs187238 (-137G>C) SNPs as genetic determinants of the observed variability in IL18 expression. FAU - Dziedziejko, Violetta AU - Dziedziejko V AD - Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland. FAU - Kurzawski, Mateusz AU - Kurzawski M FAU - Paczkowska, Edyta AU - Paczkowska E FAU - Machalinski, Boguslaw AU - Machalinski B FAU - Pawlik, Andrzej AU - Pawlik A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120620 PL - Poland TA - Postepy Hig Med Dosw (Online) JT - Postepy higieny i medycyny doswiadczalnej (Online) JID - 101206517 RN - 0 (Interleukin-18) RN - 0 (RNA, Messenger) SB - IM MH - Alleles MH - Female MH - Gene Expression MH - Genotype MH - Heterozygote MH - Homozygote MH - Humans MH - Interleukin-18/*genetics/*metabolism MH - Leukocytes, Mononuclear/*metabolism MH - Male MH - *Polymorphism, Single Nucleotide MH - RNA, Messenger/*metabolism EDAT- 2012/08/28 06:00 MHDA- 2013/05/03 06:00 CRDT- 2012/08/28 06:00 PHST- 2012/08/28 06:00 [entrez] PHST- 2012/08/28 06:00 [pubmed] PHST- 2013/05/03 06:00 [medline] AID - 1000980 [pii] AID - 10.5604/17322693.1000980 [doi] PST - epublish SO - Postepy Hig Med Dosw (Online). 2012 Jun 20;66:409-14. doi: 10.5604/17322693.1000980.