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

Date Published: July 11, 2017

Publisher: Public Library of Science

Author(s): Chung-Ming Huang, Hsin-Han Chen, Da-Chung Chen, Yu-Chuen Huang, Shih-Ping Liu, Ying-Ju Lin, Yuan-Yen Chang, Hui-Wen Lin, Shih-Yin Chen, Fuu-Jen Tsai, Joseph Devaney.


We have previously described the association of rheumatoid arthritis (RA) prevalence and two epidermal growth factor receptor (EGFR) SNPs (rs17337023 and rs2227983) among the Taiwanese population. This present study aimed to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA.

The cohort study included 366 Taiwan’s Han Chinese RA patients and 326 age and gender matched healthy controls. Blood samples collected from the participants were analyzed to determine their serum EGFR levels and to identify EGFR SNPs from their genomic DNA. Genotyping for EGFR SNPs was performed by restriction fragment length polymorphism (RFLP) assay. The relationship between EGFR SNP and the clinical manifestations of RA was evaluated.

Our results showed that a statistically significant difference in genotype frequency distributions at rs17337023 SNP for RA patients and controls (p ˂ 0.05). In addition, compared with the haplotype frequencies between case and control groups, the RA patient with the GT haplotype appeared to be a significant “protective” haplotype compared with other haplotypes (OR: 0.73, 95% CI: 0.59–0.91; p = 0.005). Furthermore, the increased serum level of EGFR was also observed in RA patients (p ˂ 0.001).

Our study showed that RA is associated with rs17337023 SNP in EGFR gene and increased serum level of the EGFR protein. These findings suggest EGFR is worthy of further investigation as a therapeutic target for RA.

Partial Text

Rheumatoid arthritis (RA) is an autoimmune disease in which the body’s defense system attacks every part of the body, particularly the synovial joints. This can result in a chronic and systemic inflammatory condition and can lead to disability if the patient is not properly treated. Although the exact causes of RA are not fully known, most scientists think that a combination of genetic traits and environmental triggers are responsible for causing the disease. RA affects nearly 1% of the population worldwide [1–3] and seems to affect females three times more likely than men. The prevalence of RA increases with age and is more common among people between 40 to 65 years old of age. In Taiwan, Chinese men and women have overall lower prevalence and incidence rates than many other countries [4,5]. But similar to other countries, RA patients in Taiwan also have higher mortality than the general population, particularly those who suffer from RA-related complications. RA imposes a huge social and economic burden on the national social welfare and healthcare systems [1,5–9]. In advanced cases, patients with joint deformities require not only medical and surgical care, but also rehabilitation and psycho-social support.

The severity of RA varies greatly from person to person. The exact cause of RA is unknown and is a very active area of global research. We performed a candidate gene study in order to investigate the association of genetic variants in EGFR, with its expression, and the disease severity in RA patients. EGFR was chosen as a candidate gene because EGFR polymorphisms and mutations have been associated with a number of cancers, including anal cancer [28], colorectal cancer [29], glioblastoma [30], and non-small-cell lung cancer [13,16]. RA is characterized by proliferative and invasive synovial fibroblasts in the synovium [3,10,22], which are a population of cells with properties similar to cancer cells. We investigated the association of SNPs tagging EGFR with its serum level and RA severity in a Taiwan’s Han Chinese study cohort.




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