Genetic and functional evaluation of an interleukin-12 polymorphism (IDDM18) in families with type 1 diabetes

Bergholdt, Regine; Ghandil, Pegah; Johannesen, Jesper; Kristiansen, OP; Kockum, Ingrid; Luthman, Holger; Rønningen, K. S.; Nerup, Jørn; Julier, Cécile; Pociot, Flemming

doi:10.1136/jmg.2003.010454

Cited by 36 publications

(30 citation statements)

References 33 publications

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“…Although there are conflicting reports on the relationship between the SNP and functional IL-12 gene expression on cell lines [28,33], Yilmaz et al [29] reported that LPS and PPD stimulation of PBML have induced higher levels of IL-12 in CC homozygotes in vitro. Bergholdt et al [34] also reported the higher secretion of IL-12 by stimulation of PBML with IFNγ and LPS. The present study, however, showed no association of the elevated levels of serum IL-12 in hyperthyroid phase of GD with the genotypes of the IL-12B gene polymorphism.…”

Section: Discussionmentioning

confidence: 91%

“…Numerous single nucleotide polymorphisms (SNP) have recently been identified in the IL-12B gene [27] and the 1188A/C polymorphism in the 3' untranslated region (3'UTR) of the IL-12B gene is associated with IL-12B mRNA expression levels [28] and IL-12 secretion levels from lipopolysaccharide (LPS) and purified protein derivative (PPD) stimulated peripheral blood mononuclear lymphocytes (PBML) [29]. Further, IL-12B gene has been proposed as a susceptibility gene in type 1 diabetes mellitus [28,30,31] with controversy [32][33][34], asthma [35] and hepatitis C virus infection [36]. Thus, IL-12B gene might be a potential candidate gene contributing to the development of GD or influencing its clinical course.…”

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confidence: 99%

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Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

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Abstract. Graves' disease (GD) is an autoimmune disorder with genetic predisposition and frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is an important mediator of inflammatory immune responses and is expressed in the thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is located at chromosome 5q31-33. The aim of the present study was to investigate whether IL-12B gene polymorphism is associated with the development of GD or GO. IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the 3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the polymerase chain reaction -restriction fragment length polymorphism method. There was no difference in allele or genotype frequency of the IL-12B gene polymorphism (1188A/C) between GD patients and control subjects. There was no association of the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or serum IgE levels. There was no association of the IL-12B gene polymorphism with serum IL-12 levels, which were significantly elevated in hyperthyroid phase of GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or GO susceptibility in Japanese.

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Section: Discussionmentioning

confidence: 91%

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confidence: 99%

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

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“…This susceptibility locus was named IDDM18, and IL-12B alleles were differently expressed in Epstein-Barr virus (EBV) cell lines. However, a study of Danish, European, and American families could not confirm any association, although the correlation of IL-12 alleles and expression showed a trend of a higher IL-12 secretion in the presence of the 1159C allele (Bergholdt et al 2004). Still, a genome scan finds little support of the IDDM18 locus on chromosome 5q33, with a maximum logarithm of odds (LOD) score of just below 1 (Concannon et al 2005), which may be due to the fact that susceptibility is either weak or operational in some populations only.…”

Section: Discussionmentioning

confidence: 99%

TIM-3 polymorphisms in type 1 diabetes families

et al. 2008

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“…The rs3212227 polymorphism of the 3' untranslated region (3' UTR) of the IL12B gene was evaluated with the polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) assay for the rs3212227 as described previously [28].…”

Section: Methodsmentioning

confidence: 99%

Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy

et al. 2011

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In diabetic retinopathy (DR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, and angiogenic factors are present. We investigated the hypothesis that rs2243250 polymorphism of the interleukin 4 (IL-4) gene or rs1800896 polymorphism of the interleukin 10 (IL-10) gene, and rs3212227 polymorphism of the 3’ untranslated region (3’ UTR) of the interleukin-12 p40 gene (IL12B) may be associated with the development of proliferative diabetic retinopathy (PDR) in Caucasians with type 2 diabetes (DM2). This cross sectional case — control study included 189 patients with PDR and 187 patients with type 2 diabetes without PDR. Polymorphisms rs1800896 of the IL-10 gene, rs2243250 of the IL-4 gene, and rs3212227 of IL12B gene were analyzed by ARMS -PCR and RFLP -PCR methods. Multivariate analysis demonstrated the GG genotype of the rs1800896 polymorphism of the IL-10 gene to be associated with increased risk for PDR (OR=1.99; 95% CI=1.11–3.57; P=0.02), whereas the TT genotype of the rs2243250 polymorphism of the IL-4 gene and the AA genotype of the rs3212227 polymorphism of the IL-12 gene were not independent risk factors for PDR. Our findings suggest that the genetic variations at the IL-10 promoter gene might be a genetic risk factor for PDR in Caucasians with type 2 diabetes.

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Genetic and functional evaluation of an interleukin-12 polymorphism (IDDM18) in families with type 1 diabetes

Cited by 36 publications

References 33 publications

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

TIM-3 polymorphisms in type 1 diabetes families

Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy

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