Association of Single Nucleotide Polymorphisms in the IL‐18 Gene with Production of IL‐18 Protein by Mononuclear Cells from Healthy Donors

Abstract

IL-18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL-18 production are found in the gene promoter region. We investigated the association of SNPs in the IL-18 promoter at −607 and −137 with the level of IL-18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL-18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS-stimulated IL-18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL-18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL-18 gene influence the level of IL-18 protein production by PBMC from healthy donors in Southwestern Siberia.

IL-18 105 A>C polymorphism contributes to renal manifestations in patients with SLE

“…Results from linkage disequilibrium investigations indicate a significant association between IL-18 -137 G>C and IL-18 105 A>C polymorphic variants [34,40]. Moreover, individuals bearing the IL-18 AA genotype exhibited a higher production of this cytokine than subjects bearing either the AC or CC genotype [34].…”

“…Many polymorphic variants in IL-18 promoter regions influence expression of IL-18 and may affect the blood plasma level of IL-18 [22,34,40]. It has been reported that single nucleotide polymorphisms in the IL-18 gene promoter at −607 C→A and −137 G→C alter the affinity of binding sites for CREB transcriptional factors and the H4TF-1 nuclear factor [22].…”

“…It has been reported that single nucleotide polymorphisms in the IL-18 gene promoter at −607 C→A and −137 G→C alter the affinity of binding sites for CREB transcriptional factors and the H4TF-1 nuclear factor [22]. The allele −137G is associated with increases in both spontaneous and stimulated IL-18 biosynthesis [34,40].…”

IL16 and IL18 gene polymorphisms in women with gestational diabetes

“…It has been shown that IL18 promoter gene polymorphisms rs187238 and rs1946518, may influence promoter activity and IL18 production [12,16,17]. Previous studies have indicated that IL16 and IL18 are pro-inflammatory cytokines involved in the pathogenesis of diabetes [13,[18][19][20].…”

Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis

“…On the other hand, we can assume that homozygotes for the allele are the lowest producers of the cytokine and heterozygotes are the highest producers of the cytokine. Khripko et al (2008) Values are given as number (%)…”