The Interaction Between Allelic Variants ofCD86andCD40LG: A Common Risk Factor of Allergic Asthma and Rheumatoid Arthritis

Abstract

PurposeAllergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance-related diseases, and immune tolerance is known to be influenced by costimulatory molecules. In this study, we sought to identify common genetic susceptibility in AA and RA.MethodsTwo hundred cases of AA, 184 cases of RA, and 182 healthy controls were recruited at the Seoul National University Hospital, Seoul, Korea. Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, -3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and genetic interactions were evaluated by multifactor dimensionality reduction (MDR) analysis.ResultsMDR analysis revealed a significant gene-gene interaction between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be significantly more likely to develop AA than those with the T/T genotype of -3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89-12.98; logistic regression analysis controlled by age). Similarly those subjects showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01-107.00, logistic regression analysis controlled by age).ConclusionsOur findings suggest that a genetic interaction between CD86 and CD40LG favors the development of both AA and RA.

Association between CD40 rs1883832 and immune-related diseases susceptibility: A meta-analysis

“…The selection process was shown in Figure 1 . 11 full-text articles were excluded (2 duplicate study [ 63 , 64 ]; 3 detailed genotype data could not be extracted and might from the same population of another study [ 14 – 16 ]; 4 improper full text [ 17 – 20 ]; 2 might from the same population of a larger study [ 21 , 22 ]). Finally, 40 articles [ 23 – 62 ] were included in our meta-analysis.…”

Genetic variants in the PSMA6, PSMC6 and PSMA3 genes associated with childhood asthma in Latvian and Taiwanese populations

“…Due to the pleiotropic effect, a frequent phenomenon in human complex traits and diseases [36], some loci of susceptibility may be shared among many autoimmune and other immune-mediated diseases [37,38]. Earlier the genetic pleiotropic effect has been reported for asthma and obesity [39,40] and for asthma and juvenile rheumatoid arthritis [41,42]. Similarly, SNPs associated with asthma in our current study, previously have been found to be susceptible in Latvians to other immune-mediated pathologies including juvenile idiopathic arthritis [24,43], children obesity [44] and multiple sclerosis [45].…”

The Influence of Genetic Variations in the CD86 Gene on the Outcome after Allogeneic Hematopoietic Stem Cell Transplantation

“…Moreover, in another immune tolerance-related disease, like asthma [ 24 ], the authors made hypothesis that the CD86 gene, as a part of the vitamin D pathway, is associated with susceptibility to the disease; especially, the rs2715267 SNP was associated with the modest risk of atopy and asthma. Also, for rheumatoid arthritis (RA) [ 25 ], this SNP together with −3458A>G CD40LG polymorphism was associated with the risk of RA. On the basis of in silico analysis, Lee et al [ 25 ] postulated that predicted binding motifs for CD86 rs2715267 are SRF, ELF3, TCF3, TCF7, TCF7L2, and ZFP105, but these speculations were not confirmed by any in vitro study.…”

“…Also, for rheumatoid arthritis (RA) [ 25 ], this SNP together with −3458A>G CD40LG polymorphism was associated with the risk of RA. On the basis of in silico analysis, Lee et al [ 25 ] postulated that predicted binding motifs for CD86 rs2715267 are SRF, ELF3, TCF3, TCF7, TCF7L2, and ZFP105, but these speculations were not confirmed by any in vitro study.…”