IL-18 gene polymorphisms affect IL-18 production capability by monocytes

Arimitsu, Junsuke; Hirano, Tôru; Higa, Shinji; Kawai, Masao; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Hagiwara, Keisuke; Ohgawara, Tomoharu; Kuwabara, Yusuke; Kawase, Ichiro; Tanaka, Toshio

doi:10.1016/j.bbrc.2006.02.096

Cited by 100 publications

(98 citation statements)

References 19 publications

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“…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].…”

Section: Discussionmentioning

confidence: 96%

“…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].…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

Section: Discussionmentioning

confidence: 99%

“…Although this polymorphism does not result in amino acid changes, individuals with IL-18 AA, AC and CC genotypes differ in production of this cytokine [34]. Therefore, we analysed the distribution of IL-18 105 A>C polymorphic variants in SLE patients (n=111) and controls (n=152).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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SummarySystemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by various aberrations including increased production of IL-18.Since IL-18 105 A>C polymorphic variants have been linked to increased production of this cytokine, we investigated the prevalence of IL-18 105 A>C (rs549908) polymorphic variants in SLE patients (n=111) and controls (n=152).There were no significant differences in the distribution of IL-18 105 A>C polymorphic variants in SLE patients and controls. However, there was a significant association between the IL-18 105 AA genotype (recessive model) and renal manifestations OR=3.360 (1.523-7.415, P=0.0039) and the P value remained statistically significant after Bonferroni correction (P corr = 0.0351).Our findings indicate that the IL-18 105 AA genotype variant can contribute to renal manifestations in patients with SLE.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…1,2 Variation in the IL18 gene has been shown to influence circulating levels of IL-18, 3-6 is associated with risk for various inflammatory diseases including cardiovascular disease (CVD), [7][8][9] and affects production of IL-18 by monocytes. 10,11 Though the distribution of genetic variation in IL18 in populations of recent European origin has been examined, little is known about populations more globally. We have therefore investigated the distribution across Africa by determining the frequency of potentially informative haplotypes and compared the results with populations from neighbouring regions and the UK.…”

Section: Interleukin (Il)-18 Is a Pleiotropic Cytokine Involved In Bomentioning

confidence: 99%

The frequency of an IL-18-associated haplotype in Africans

Thompson¹,

Humphries

Thomas

et al. 2012

Eur J Hum Genet

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Variation within the gene for the proinflammatory cytokine interleukin (IL)-18 has been associated with inter-individual differences in levels of free protein and disease risk. We investigated the frequency of function-associated IL18 gene haplotypes in an extensive sample (n ¼ 2357) of African populations from across the continent. A previously identified five tagging SNP (single-nucleotide polymorphism) haplotype (here designated hGTATA), known to be associated with lower levels of IL-18, was observed at a frequency of 27% in a British population of recent European ancestry, but was found at low frequency (o8%) or completely absent in African populations. Potentially protective variants may, as a consequence, be found at low frequency in African individuals and may confer a difference in disease risk.

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Joint Analysis of SNPs and Proteins Identifies RegulatoryIL18Gene Variations Decreasing the Chance of Spastic Cerebral Palsy

et al. 2012

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Cerebral palsy (CP) is a permanent disorder, affecting 2-3 per 1,000 live born children, disturbing movement and posture. Spastic limbs affects about 70-80% of the CP children, and this group is the target of our study. CP is considered a multifactorial condition believed to be provoked by, for example, preterm birth, infection during pregnancy, neural disorders, and genetics, to mention some. Interestingly, the cytokine network is believed to be involved in many of these disorders. In this study, including 203 spastic CP cases and 167 controls, we measured the levels of 25 cytokine proteins, and genotyped 159 SNPs in their gene loci. Using logistic regression, we estimated the genetic association of SNP genotypes to spastic CP. In addition, fitting a Tobit regression model for each protein and each SNP in the respective gene loci, we estimated three regression coefficients corresponding three different effects of the genetic variation on the protein level. Intriguingly, two IL18 loci SNPs (rs549908:A>C and rs1290349:C>A) showed a protective effect against spastic CP, and interestingly both were associated to a decreased epidemiological expression of IL-18 protein. By joining protein data to genetic information, we have provided new data suggesting IL18's involvement in the pathogenesis of spastic CP.

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IL-18 gene polymorphisms affect IL-18 production capability by monocytes

Cited by 100 publications

References 19 publications

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

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

The frequency of an IL-18-associated haplotype in Africans

Joint Analysis of SNPs and Proteins Identifies RegulatoryIL18Gene Variations Decreasing the Chance of Spastic Cerebral Palsy

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