Association of rheumatoid arthritis risk with EGFR genetic polymorphisms in Taiwan’s Han Chinese population

Abstract

The involvement of the epidermal growth factor receptor (EGFR) in the pathogenesis of cancer is well documented. In contrast, its role in rheumatoid arthritis (RA) development is not that well defined although previous studies suggested the possible link between autoimmune diseases and malignancy. Therefore, we aimed to examine whether there is a link between the EGFR genetic polymorphisms and the RA. Our study gauged the effects of EGFR (rs11543848 and rs17337023) single-nucleotide polymorphisms (SNPs) on RA among Taiwan's Han Chinese population. Polymorphism of EGFR gene was analyzed in 188 RA patients and 128 control subjects. Genotyping for EGFR SNPs was performed by restriction fragment length polymorphism (RFLP) assay. Our data confirmed statistically significant increased risk of RA development in subjects with A carrier at rs17337023 SNP (P < 0.0001), and subjects with A allele at rs17337023 SNP (odds ratio [OR] = 1.52; 95% confidence interval [CI] = 1.10-2.09). Furthermore, comparison of haplotype frequencies between patients and controls suggested GA and AT haplotypes were more "at-risk" for RA development (P < 0.0001 and P < 0.01, respectively). However, comparisons of the clinical features of RA patients according to different genotypes and haplotypes revealed no significant difference. In conclusion, our data yield the new information on EGFR polymorphisms (rs11543848 and rs17337023) with the susceptibility of RA development and polymorphism revealed by this study merit further investigation.

Fibroblast-Like Synoviocytes Induce Calcium Mineral Formation and Deposition

“…The genes displaying decreased expression also included epidermal growth factor receptor (EGFR: −5.57-fold), connective tissue growth factor (CTGF: −4.99-fold), adrenergic beta-2 receptor (ADRB2: −4.45-fold), transforming growth factor beta 1 (TGF- β 1: −2.16-fold), bone morphogenetic protein 6 (BMP6: −3.49-fold), and tumor necrosis factor receptor superfamily member 11a (TNFRSF11A/RANK: −2.35-fold). The majority of these genes have been previously implicated in RA [40–45]. …”

Rheumatoid arthritis is associated with rs17337023 polymorphism and increased serum level of the EGFR protein

“…For this study, we enrolled 366 RA patients and 326 healthy subjects from China Medical University Hospital in Taiwan. As described in detail previously [23], section material and methods. Patients with RA were recruited based on the 1987 revised criteria of the America College of Rheumatology [24].…”

“…In the study of the EGFR rs2227983 SNP, the primers used were PCR amplification was performed in a PCR thermal cycler (GeneAmp PCR System 2400, Perkin Elmer). The PCR cycling conditions for EGFR rs2227983 SNP examination were as described in detail previously [23], section material and methods. The EGFR rs2227983 SNP was analyzed by PCR amplification, followed by restriction enzyme analysis with BstNI.…”

“…EGFR has been proposed as a valuable therapeutic target for the treatment of joint inflammation in patients with RA. We have previously described the association of rheumatoid arthritis prevalence and two single nucleotide polymorphism sites (SNPs, rs11543848, which has now merged into rs2227983 and rs17337023) of EGFR among Taiwan’s Han Chinese population [23]. This present study we increased the sample size of the cohort and aimed to elucidate whether the SNPs, can alter the expression of EGFR in the progression of RA.…”

Accelerated and increased joint damage in young mice with global inactivation of mitogen-inducible gene 6 after ligament and meniscus injury

“…EGFR signaling is involved in diseases that affect cartilage. In humans, there is a significant increase in the risk of RA development with the occurrence of the single-nucleotide polymorphism rs17337023 in EGFR , and arthritic joints have increased EGFR2 protein in the synovial fluid and membrane [17,18]. Pharmacological inhibition of EGFR can reduce the severity of collagen-induced RA in mice, and the inhibition of EGFR by adenovirus can reduce joint damage in arthritic mice [19,20].…”