Huang Chung-Ming, Chen Hsin-Han, Chen Da-Chung, Huang Yu-Chuen, Liu Shih-Ping, Lin Ying-Ju, Chang Yuan-Yen, Lin Hui-Wen, Chen Shih-Yin, Tsai Fuu-Jen
School of Chinese Medicine, China Medical University, Taichung, Taiwan.
Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
PLoS One. 2017 Jul 11;12(7):e0180604. doi: 10.1371/journal.pone.0180604. eCollection 2017.
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.
我们之前已经描述了台湾人群中类风湿性关节炎(RA)患病率与两个表皮生长因子受体(EGFR)单核苷酸多态性(SNP,即rs17337023和rs2227983)之间的关联。本研究旨在阐明这些SNP是否会在RA进展过程中改变EGFR的表达。
队列研究纳入了366名台湾汉族RA患者以及326名年龄和性别相匹配的健康对照。对从参与者采集的血样进行分析,以测定其血清EGFR水平,并从其基因组DNA中鉴定EGFR SNP。通过限制性片段长度多态性(RFLP)分析对EGFR SNP进行基因分型。评估EGFR SNP与RA临床表现之间的关系。
我们的结果显示,RA患者和对照在rs17337023 SNP的基因型频率分布上存在统计学显著差异(p<0.05)。此外,与病例组和对照组之间的单倍型频率相比,携带GT单倍型的RA患者与其他单倍型相比似乎是一种显著的“保护性”单倍型(比值比:0.73,95%置信区间:0.59 - 0.91;p = 0.005)。此外,在RA患者中还观察到EGFR血清水平升高(p<0.001)。
我们的研究表明,RA与EGFR基因中的rs17337023 SNP以及EGFR蛋白血清水平升高有关。这些发现表明,EGFR作为RA的治疗靶点值得进一步研究。