Interleukin 12 (IL12B), interleukin 12 receptor (IL12RB1) and interleukin 23 (IL23A) gene polymorphism in systemic lupus erythematosus

Sánchez, Elena; Morales, Sergio Rodríguez; Paco, Laura; Ma, Li-na; Hidalgo, Carmen; Jiménez-Alonso, J; Torres, Belén; Ma, Genshan; Callejas, José Luis; Ortego-Centeno, Norbérto; Sánchez-Román, Julio; González-Escribano, Marı́a-Francisca; Martin, Jose-Ezequiel

doi:10.1093/rheumatology/keh697

Cited by 33 publications

(31 citation statements)

References 28 publications

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“…Our present results are different from findings in other population showing lack of association of IL12Bpro polymorphisms with SLE incidence [18]. Possible explanations of this discrepancy could be the variety of the genetic contributions in different ethnicities derived from different ancestral groups, as well as the gene interactions between IL12B polymorphisms and other loci.…”

Section: Discussioncontrasting

confidence: 99%

“…However, no significant associations between other investigated polymorphism in cis-regulatory region of IL12B gene, a substitution of A to C at position ?16,974 in 3 0 UTR, and SLE were observed. Previous study had shown that both polymorphisms in IL12B may not play a relevant role in the susceptibility or disease expression of SLE in the Spanish population [18]. Recently, a weak association was observed between A-allele of SNP in 3 0 UTR of IL12B gene in SLE patients with proteinuria among Thais population [19].…”

Section: Discussionmentioning

confidence: 97%

“…However, there are only two studies which investigated the association of IL12B gene polymorphisms and pathogenesis of SLE among Spanish and Thais patients [18,19]. Sanchez et al [18] suggested that IL12B 3 0 UTR SNP and IL12Bpro polymorphism do not play a relevant role in the susceptibility or severity of SLE, although a weak association between carrying of A-allele from IL12B 3 0 UTR SNP and lupus nephritis has been reported. Independently, other authors have found an association between the carrying of same allele and proteinuria among SLE patients [19].…”

Section: Introductionmentioning

confidence: 99%

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Functional genetic polymorphisms in interleukin-12B gene in association with systemic lupus erythematosus

et al. 2010

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Genetic polymorphisms in cytokine genes, which influence gene expression, may have an important impact on SLE susceptibility and severity. The aim of this study was to examine the possible influence of two functional polymorphisms in cis-regulatory regions of IL12B gene in the susceptibility and clinical symptoms of SLE in Bulgarian patients. Female SLE patients (n = 141) and 124 healthy women were included in the study. Genotyping for the IL12B A/C polymorphism in 3'UTR was performed by restriction fragment length polymorphisms PCR assay and for the IL12Bpro polymorphism by allele-specific PCR. Genotype-22 of IL12Bpro polymorphism was overrepresented among women with SLE (28 vs. 17%; OR = 1.875; 95% CI: 1.037 ÷ 3.390; P = 0.037). Respectively, a higher frequency of allele-2 was found in patients than in controls (51% vs. 40%; OR = 1.566; 95% CI: 1.110 ÷ 2.210; P = 0.011). Also, we found significantly elevated frequency of genotype-22 of IL12Bpro polymorphism among SLE patients who were simultaneously carrier of genotype-AA of SNP in 3'UTR. Women with both homozygous genotypes, genotype-AA of SNP in 3'UTR and genotype-22 of IL12Bpro polymorphism, had a 2.1-fold significantly elevated risk for SLE development. The carrying of genotype-11 of IL12Bpro polymorphism was positively associated with hematological and neuropsychiatric manifestations of SLE. We have provided evidence that the IL12Bpro polymorphism was associated with SLE development among Bulgarian women. Although a strong individual effect of SNP in 3'UTR of IL12B was not detected, we found that genotype-22 of IL12Bpro was predominantly combined with genotype-AA of SNP in 3'UTR among SLE patients and this combination elevates the risk of SLE.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Functional genetic polymorphisms in interleukin-12B gene in association with systemic lupus erythematosus

et al. 2010

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“…Besides, the combination of the IL-12B rs17860508 GC allele and/or IL-12B rs3212227 C allele increased the risk of SLE and/or the severity of SLE parameters in Polish population [45]. Other studies have showed that C allele in IL-12B 3′ UTR connected with higher production of IL-12p70 while GC allele in IL-12B promoter binding with Sp1 increased gene transcription and cytokine activity [46][47][48][49][50][51][52]. All these alleles might increase the levels of IL-12 and affect the immune response via regulation of T cell activity, resulting in abnormalities in SLE.…”

Section: Il-12 and Its Regulatory Roles In Slementioning

confidence: 98%

“…Past studies have revealed that synthetic oligodeoxynucletides (ODN) with TTAGGG motif, which highly accumulated in telemeric region of mammalian chromosomes, could be suppressed to treat autoimmune disease [50][51][52]. Sano et al reported that ODN without CpG motifs functioned as an adjuvant to induce Th2 differentiation and Dong et al reported that glomerulonephritis and survival of lupus mice model were improved by synthetic ODN with significant reduction of anti-ds DNA auto-antibody, IL-12, IFN-γ and IL-6.…”

Section: Il-12 and Ifn-γ Targeted Therapy For Slementioning

confidence: 99%

Biological Features of IL-12 and IFN-? in the Pathogenesis of Systematic Lupus Erythematosus

Lu¹,

Wang²,

Wang³

et al. 2017

J Clin Exp Pathol

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Systemic lupus erythmatosus is a chronic autoimmune disease characterized by abnormal immune response with overproduction of auto-antibodies, self-destructive complexes and hyperactivity of both T and B lymphocytes. Although the exact pathogenesis of SLE remains unclear, it has been found that the imbalance of Th1/Th2, subsequent cytokines and anti-or pro-inflammatory mediators could reflect the stage and phenotype of SLE. Among diverse cytokines involved in the disease progression, IL-12 and IFN-γ gain much attention for their biological functions in SLE. There existed many divergences on the expression level of IL-12 while few conflicts were demonstrated on elevated level of IFN-γ in SLE patients. By analysis of gene polymorphisms, it was suggested that positive correlations were observed between IL-12B rs3212227, IL-12B rs17860508 and susceptibility to and severity of SLE in Polish patients. In addition, the combination of the IL-12B rs17860508 GC allele and/or IL-12B rs3212227 C allele could increase the risk of SLE progression and/or severity of SLE parameters in Polish population. Furthermore, it was also found that the incorporation of IFN-γ R 1 Met 14/Val 14 and IFN-γ R 2 Gln 64/Gln 64 genotypes was a potential risk factor for SLE. Based on the previous researches, IL-12 and IFN-γ targeted gene therapy was developed and found to be effective in murine lupus. Intramuscular injection of IFN-γR/IgG1Fc fusion protein encoded cDNA and suppressive ODN was found to decrease the severity of disease and promote survival of lupus mice. On the other hand, intramuscular injection of IL-12 and IL-18 encoded plasmids alone or together was also observed to have therapeutic effects on murine lupus. All in all, this review mainly introduces the biological features and the potential therapeutic effects of IL-12 and IFN-γ in the pathogenesis of SLE.

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Confirmation of an association between rs6822844 at the Il2–Il21 region and multiple autoimmune diseases: Evidence of a general susceptibility locus

Maiti¹,

Kim-Howard²,

Viswanathan³

et al. 2010

Arthritis & Rheumatism

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Objective. Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2-IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in nonEuropean populations, and to perform disease-specific and overall meta-analyses using data from previously published studies.Methods. We evaluated case-control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta-analyses were performed using data from the present study and previous studies.Results. We detected significant associations of rs6822844 with SLE (P ‫؍‬ 0.008), type 1 DM (P ‫؍‬ 0.014), RA (P ‫؍‬ 0.019), and primary SS (P ‫؍‬ 0.033) but not with BD (P ‫؍‬ 0.34) or CD (P ‫؍‬ 0.98). We identified little evidence of population differentiation (F ST ‫؍‬ 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease-specific meta-analysis indicated significant association for RA (P meta ‫؍‬ 3.61 ؋ 10 ؊6 ), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (P meta ‫؍‬ 3.48 ؋ 10 Conclusion. Our results indicate that there is an association between rs6822844 and multiple autoimmune diseases in non-European populations. Metaanalysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations.Genetic susceptibility plays an important role in autoimmune diseases.

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Interleukin 12 (IL12B), interleukin 12 receptor (IL12RB1) and interleukin 23 (IL23A) gene polymorphism in systemic lupus erythematosus

Abstract: These results suggest that polymorphisms located in IL12B, IL12RB1 and IL23A genes may not play a relevant role in the susceptibility or severity of SLE in the Spanish population.

Cited by 33 publications

References 28 publications

Functional genetic polymorphisms in interleukin-12B gene in association with systemic lupus erythematosus

Functional genetic polymorphisms in interleukin-12B gene in association with systemic lupus erythematosus

Biological Features of IL-12 and IFN-? in the Pathogenesis of Systematic Lupus Erythematosus

Confirmation of an association between rs6822844 at the Il2–Il21 region and multiple autoimmune diseases: Evidence of a general susceptibility locus

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