A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression: implications for the pathogenesis

Vazgiourakis, Vassilios; Zervou, Maria I.; Choulaki, Christianna; Βertsias, George; Melissourgaki, Maria; Yılmaz, Neslihan; Sidiropoulos, Prodromos; Plant, Darren; Trouw, Leendert A.; Toes, René E. M.; Kardassis, Dimitris; Yavuz, Şule; Boumpas, Dimitrios T.; Goulielmos, George N.

doi:10.1136/ard.2010.146530

Cited by 55 publications

(61 citation statements)

References 46 publications

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“…These factors may have limited our analysis. An association between the minor T allele of rs4810485 and down-regulation of CD40 mRNA has been previously described (Vazgiourakis et al, 2011). However, conflicting results have been obtained regarding the rs1883832 SNP.…”

Section: Discussionmentioning

confidence: 76%

“…The CD40 SNPs rs1883832 and rs4810485 have been identified as susceptibility markers for this and other autoimmune diseases, such as GD (Tomer et al, 2002;Kim et al, 2003;Li et al, 2012), MS (Blanco-Kelly et al, 2010;Sokolova et al, 2013), and SLE (Vazgiourakis et al, 2011;Chen et al, 2015;Lee et al, 2015). In addition, several studies suggest that these polymorphisms affect CD40 expression at the mRNA and protein level (Jacobson et al, 2005;Vazgiourakis et al, 2011;Field et al, 2015;Wagner et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Although the T allele of rs1883832 has been associated with increased susceptibility to MS and SLE among Russian and Chinese individuals, respectively (Sokolova et al, 2013;Chen et al, 2015), it has also been reported to have a protective effect for RA in the Spanish population (García-Bermúdez et al, 2012). Meanwhile, rs4810485, located in the second intron of CD40, is thought to affect CD40 mRNA and protein expression in B cells and monocytes (Vazgiourakis et al, 2011). Interestingly, the minor allele of this SNP is associated with breast cancer risk in the Chinese population (Shuang et al, 2011), whereas among Europeans, it has been suggested to be protective for the development of RA (Orozco et al, 2010;Lee et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Other non-HLA risk loci for RA, including the CD40 gene, have been identified based on genome-wide association studies and meta-analysis (Wellcome Trust Case Control Consortium, 2007;Raychaudhuri et al, 2008;Perricone et al, 2011;Suzuki et al, 2011). Interestingly, CD40 has been implicated in other autoimmune diseases, such as multiple sclerosis [MS; Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene), 2009], Grave's disease (GD; Li et al, 2012), systemic lupus erythematosus (SLE; Vazgiourakis et al, 2011), and Crohn's disease (Blanco-Kelly et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients from western Mexico

et al. 2016

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ABSTRACT. The CD40 pathway is involved in the development and pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). Two single nucleotide polymorphisms (SNPs) in the CD40 gene, rs1883832 and rs4810485, are associated with susceptibility to inflammatory and autoimmune diseases and are thought to alter CD40 expression at the mRNA and protein level. This study assessed for the first time the association of these SNPs with RA and CD40 mRNA levels in a western Mexican population. A total of 278 RA patients and 318 control subjects were included. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and CD40 mRNA expression was determined by realtime quantitative PCR. No significant differences in genotype and allele frequencies were identified between the RA patients and controls. When stratified by genotype, these SNPs were not found to be associated with the presence of autoantibodies or the clinical activity of the disease. CD40 mRNA levels were elevated 1.5-fold in RA patients compared to control subjects; however, no clear tendencies were observed following stratification by genotype. These results suggest that the CD40 SNPs rs1883832 and rs4810485 are not RA susceptibility markers in the western Mexican population. Further studies are needed to clarify their roles in CD40 mRNA expression.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients from western Mexico

et al. 2016

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“…28,29 The associated SNPs of these genes for KD and these diseases are identical or belonging to the same SNP group of high linkage disequilibrium. By bioinformatics analyses integrating published GWAS results and information of gene expression, expression quantitative trait loci and epigenome, Farh et al suggested the importance of Blinage cells in KD pathogenesis.…”

Section: Development Of Genetic Research Findings Novel Insights Intomentioning

confidence: 99%

The genetics of Kawasaki disease

Onouchi

2017

Int J of Rheum Dis

102

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Kawasaki disease (KD) is a complex disorder which affects genetically susceptible infants and children. Several susceptibility genes (e.g., ITPKC, CASP3, CD40 and ORAI) and chromosomal regions have been identified through genome-wide association and genome-wide linkage studies to have association with KD. Knowledge of susceptibility genes involved in the pathogenesis of KD may provide new insights into diagnosis and treatment of this condition. However, there is much that we still do not know about the genetic basis of KD.

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Association of soluble CD40 levels with ‐1 C > T CD40 polymorphism and chronic kidney disease in systemic lupus erythematosus

Tapia‐Llanos

Muñoz‐Valle

Román-Fernández

et al. 2019

Molec Gen & Gen Med

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BackgroundCD40 is a transmembrane protein mainly expressed on the antigen‐presenting cells surface. CD40 plays a crucial role in immunoglobulin class switching and antibodies production. Genetic polymorphisms in the CD40 gene have been associated with increased risk of systemic lupus erythematosus (SLE) in several populations. This study aimed to evaluate the association of CD40 polymorphisms (−1 C > T, rs1883832 and 6,048 G > T, rs4810485) with SLE susceptibility, as well as with mRNA expression and soluble CD40 (sCD40) levels.MethodsThe study included 293 patients with SLE and 294 control subjects (CS). Genotyping was performed by PCR‐RFLP method. CD40 mRNA expression was determined by quantitative real‐time PCR, and ELISA quantified sCD40 levels.ResultsThe CD40 polymorphisms −1 C > T and 6,048 G > T were associated with SLE susceptibility. There was no difference between CD40 mRNA expression and CD40 polymorphisms. The sCD40 levels were lower in SLE patients with TT haplotype, whereas higher sCD40 levels were associated with damage and impaired renal function according to SLICC and KDIGO. The sCD40 levels were negatively correlated with eGFR.ConclusionThe CD40 gene polymorphisms increase the risk of SLE in the western Mexican population. The sCD40 levels are associated with −1 C > T polymorphism and chronic kidney disease.

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A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression: implications for the pathogenesis

Cited by 55 publications

References 46 publications

CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients from western Mexico

CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients from western Mexico

The genetics of Kawasaki disease

Association of soluble CD40 levels with ‐1 C > T CD40 polymorphism and chronic kidney disease in systemic lupus erythematosus

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