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

Abstract

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.

Analysis of Genetic Variation in CD40 and CD40L: Relationship with mRNA Relative Expression and Soluble Proteins in Acute Coronary Syndrome

“…In the same line, the rs4810485 SNP was associated with CD40 protein expression on CD14 + monocytes and CD19 + B cells from lupus erythematosus patients assessed by flow cytometry [18]. Other studies have reported increased levels of sCD40 in subjects who carry the minor allele of rs1883832 and rs4810485 polymorphisms [25, 32].…”

“…The SNP on the CD40 gene, rs1883832, has been associated with ACS in the presence of the major C allele and has been related with decreased levels of sCD40 in the presence of the minor T allele and risk of cardiovascular diseases [31, 32]. In a western Mexican cohort, this was not identified as a genetic risk factor to rheumatoid arthritis (RA) [25]. This polymorphism has been associated with diminished mRNA expression of CD40 [21, 22]; rs1883832 has been found in high LD with rs4810485, the latter being significantly associated with coronary artery lesion formation in a Taiwanese population [33].…”

“…In this regard, single-nucleotide polymorphisms (SNPs) have been identified in the CD40 and CD40L genes that may increase the susceptibility for the development of ACS, through genome-wide association studies [7] and candidate gene studies [12–16]. These genetic variants have been associated with inflammatory and autoimmune diseases [17, 18], with alterations in the CD40 and CD40L mRNA expression [19–25] as well as the regulation of soluble forms modifying their function [15, 20] which have an effect in the initiation, development, and progression of atherosclerosis [26, 27].…”

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

“…For −1 C > T SNP, the following primers were used: forward 5'‐CCC CGA TAG GTG GAC CGC GAT TGG T‐3' and reverse 5'‐CCC GCC CTC TGA ACC CCC TAC CAG T‐3'; whereas for 6,048 G > T SNP the primers used were: forward 5'‐TAT TTT TGT AGT TCC TCA TTC TGG A‐3' and reverse 5'‐GCC CCC CTT TAC CTC TTT CCA‐3'. The PCR conditions were as described by Román‐Fernández et al (Román‐Fernández et al, ; Román‐Fernández, Muñoz‐Valle, & Palafox‐Sánchez, ). The amplified 505 bp PCR product containing the −1 C > T SNP was digested with 5 U of Nco I restriction enzyme (New England BioLabs ® ) at 37°C for 1 hr.…”

“…In Mexican population, the CD40 polymorphisms −1 C > T and 6,048 G > T did not found associated with rheumatoid arthritis; however, CD40 mRNA levels were 1.5‐fold higher in RA patients compared with control subjects (Román‐Fernández et al, ). This study aimed to evaluate the association between the −1 C > T and 6,048 G > T genetic variants with disease susceptibility, CD40 mRNA expression, and sCD40 levels in SLE patients.…”