Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G polymorphism in Japanese patients with type 1 diabetes

Ide, Akane; Kawasaki, Eiji; Abiru, Norio; Sun, Fuyan; Kobayashi, Masakazu; Fukushima, Tetsuya; Takahashi, Ryoko; Kuwahara, Hironaga; Kita, Atsushi; Oshima, Katsuya; Uotani, Shigeo; Yamasaki, Hironori; Yamaguchi, Yoshihiko; Eguchi, Katsumi

doi:10.1016/j.jaut.2003.10.001

Cited by 87 publications

(81 citation statements)

References 29 publications

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“…A protective effect of the À607AA diplotype was recently postulated in a case-control study of Asian RA patients, and an influence of IL-18 promoter polymorphisms on the occurrence of different inflammatory and autoimmune diseases was also suggested by several other casecontrol studies. [20][21][22][23] Our data of two separate Caucasian cohorts from Germany and Scotland showed divergent disease associations on the single-locus diplotype level, which need to be interpreted with caution in respect of the HW disequilibria observed in the respective RA cohorts. Moreover, the analyses of the compound data set were complicated by departure from HWE also in healthy controls, which was on a first glance suggestive for typing errors.…”

Section: Discussionmentioning

confidence: 71%

“…This suspicion appears as far as possible excluded by use of two independent techniques in many subjects, which gave absolutely identical results, and also by the successful use of the same method in other studies. [21][22][23][24][25] Among more theoretical explanations as genetic selection, a stratification effect by composing our two independent cohorts has to be considered here. Departure from HWE, however, required a more conservative statistical calculation of allele and diplotype associations by trend tests, which, in contrast to the exact genotype w 2 tests, failed statistical significance for both single loci.…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22][23] The IL-18 promoter and IL-18 gene represent attractive candidate regions for gene polymorphism analyses in RA given its functional role in synovitis. Therefore, we have utilized two independent cohorts of Caucasian RA patients and healthy donors (HD) for polymorphism association analysis.…”

Section: Introductionmentioning

confidence: 99%

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Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

et al. 2005

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Interleukin (IL)-18 is an important mediator of innate and adaptive immunity. We searched for an association of IL-18 promoter single-nucleotide polymorphisms (SNP) with rheumatoid arthritis (RA) in Caucasians. The entire study population was composed of two independent cohorts from Germany (n ¼ 200) and Scotland (n ¼ 410). Presence of IL-18 SNP at positions À607 and À137 was determined by allele-specific PCR in 327 RA patients and 283 healthy donors (HD). Diplotype distributions of both loci were in Hardy-Weinberg equilibrium (HWE) in the German and Scottish HD cohorts. In contrast, locus À607 was in HW disequilibrium in German, and locus À137 in Scottish RA patients. Diplotypic exact w 2 tests suggested that À607CC was overrepresented in German, and À137CC in Scottish RA patients, but conservative w 2 trend analyses could not prove any significant disease association of these single loci. SNP À607 and À137 were in strong linkage disequilibrium. The À607C*À137C haplotype was more prevalent in German RA (3.2 vs 1.2%) and in Scottish RA patients (4.1 vs 0.9%) than in the respective HD cohorts. These observations suggest that SNP of both positions contribute to the genetic background of RA pathogenesis.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

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Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

et al. 2005

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“…þ 49 G has been related to multiple diseases, including type 1 diabetes (T1D), 9 rheumatoid arthritis, 10 multiple sclerosis, 11 Graves' disease, 12 asthma, 13 or systemic sclerosis. 14 SNP À1722 has been related to lupus erythematosus in two contradictory studies, 15,16 while the À1661 G variant has been suggested to be associated with T1D.…”

Section: Introductionmentioning

confidence: 99%

Haplotype tagging efficiency in worldwide populations in CTLA4 gene

et al. 2005

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The cytotoxic T lymphocyte antigen 4 (CTLA4) acts as a potent negative regulator of T-cell response, and has been suggested as a pivotal candidate gene for autoimmune disorders such as Graves' disease, type 1 diabetes and autoimmune hypothyroidism, among others. Several single-nucleotide polymorphisms (SNPs) have been proposed as the susceptibility variants, or to be in strong linkage disequilibrium (LD) with the variant. Nevertheless, contradictory results have been found, which may be due to lack of knowledge of the genetic structure of CTLA4 and its geographic variation. We have typed 17 SNPs throughout the CTLA4 gene region in order to analyze the haplotype diversity and LD structure in a worldwide population set (1262 individuals from 44 populations) to understand the variation pattern of the region. Allele and haplotype frequency differentiation between populations is consistent with genomewide averages and points to a lack of strong population-specific selection pressures. LD is high and its pattern is not significantly different within or between continents. However, haplotype composition is significantly different between geographical groups. A continent-specific set of haplotype tagging SNPs has been designed to be used for future association studies. These are portable among populations, although their efficiency might vary depending on the population haplotype spectrum.

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“…Furthermore, there were significant differences in the À607/À137 haplotype frequencies between the two groups, suggesting there was an interaction of the two polymorphisms in conferring susceptibility to type I diabetes. 38 Ide et al 39 tested the same two promoter polymorphisms in a Japanese type I diabetic case-control study group (116 patients and 114 normal controls). They showed that À607 allele frequencies differed significantly between case and controls (P ¼ 0.023); the À607 CA genotype was present at a significantly higher proportion of case compared with control subjects (69% in case vs 57.9% in control), whereas the proportion of case subjects with the AA genotype was decreased (12.1% in case vs 26.3% in controls).…”

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confidence: 99%

Interleukin-18 genetics and inflammatory disease susceptibility

Thompson¹,

Humphries²

2007

Genes Immun

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IL18 was mapped to 11q22.2-22.3 in 1998. Owing to interleukin (IL)-18's important and novel role in immunomodulation, the gene itself has been subject to scrutiny, with the aim of discovering variants that may impact on disease susceptibility and/or progression. Despite being sequenced numerous times in different populations, no non-synonymous variants have been found. However, a number of polymorphisms within the proximal promoter have been verified that may interfere with transcriptionfactor-binding sites. Much of the subsequent association analyses have centred on these variants, but have yielded no consistent results, despite numerous different study populations being genotyped. IL18 has recently been resequenced in its entirety, enabling the tagging-single-nucleotide polymorphism (tSNP) methodology to be adopted. This approach has yielded interesting results, with genetic variation being shown to affect protein levels, and risk. This review aims to compile and reflect on the association data of interest published to date, with a focus on the diseases related to aberrant inflammatory control. Genes and Immunity (2007) 8, 91-99.

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Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G polymorphism in Japanese patients with type 1 diabetes

Cited by 87 publications

References 29 publications

Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

Haplotype tagging efficiency in worldwide populations in CTLA4 gene

Interleukin-18 genetics and inflammatory disease susceptibility

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