类风湿关节炎患者的RORC2基因变异与血清水平

RORC2 Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis.

作者信息

Paradowska-Gorycka Agnieszka, Stypinska Barbara, Pawlik Andrzej, Romanowska-Prochnicka Katarzyna, Haladyj Ewa, Manczak Malgorzata, Olesinska Marzena

机构信息

Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland.

Department of Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland.

出版信息

Int J Mol Sci. 2016 Apr 1;17(4):488. doi: 10.3390/ijms17040488.

DOI:10.3390/ijms17040488

PMID:27043554

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4848944/

Abstract

BACKGROUND

In the present study, we aimed to evaluate whether polymorphisms within the RORc2 gene are involved in the risk and severity of rheumatoid arthritis (RA).

METHODS

591 RA patients and 341 healthy individuals were examined for RORc2 gene polymorphisms. Serum retinoic acid receptor-related orphan receptor C (RORc) levels were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

The rs9826 A/G, rs12045886 T/C and rs9017 G/A RORc2 gene SNPs show no significant differences in the proportion of cases and control. Overall, rs9826 and rs9017 were in high linkage disequilibrium (LD) with D' = 0.952 and r² = 0.874, except rs9826 and rs12045886; and rs12045886 and rs9017 in weak LD. The genotype-phenotype analysis showed a significant association between RORc2 rs9826 A/G and rs9017 G/A single nucleotide polymorphisms (SNPs) and median of C-reactive protein (CRP). Serum RORc levels was higher in RA patients with rs9826AA, rs12045886TT and -TC, and rs9017AA genotypes compared to healthy subjects with the same genotypes (p = 0.02, p = 0.04 and p = 0.01, respectively). Moreover, the median of RORc protein level was higher in RA patients with number of swollen joints bigger then 3 (p = 0.04) and with Health Assessment Questionnaires (HAQ) score bigger then 1.5 (0.049).

CONCLUSIONS

Current findings indicated that the RORc2 genetic polymorphism and the RORc2 protein level may be associated with severity of RA in the Polish population.

摘要

背景

在本研究中，我们旨在评估维甲酸受体相关孤儿受体C2（RORc2）基因内的多态性是否与类风湿关节炎（RA）的风险和严重程度有关。

方法

对591例RA患者和341名健康个体进行RORc2基因多态性检测。采用酶联免疫吸附测定（ELISA）法检测血清维甲酸受体相关孤儿受体C（RORc）水平。

结果

RORc2基因单核苷酸多态性（SNP）rs9826 A/G、rs12045886 T/C和rs9017 G/A在病例组和对照组中的比例无显著差异。总体而言，除rs9826和rs12045886外，rs9826和rs9017处于高度连锁不平衡（LD）状态，D' = 0.952，r² = 0.874；rs12045886和rs9017处于弱LD状态。基因型-表型分析显示，RORc2 rs9826 A/G和rs9017 G/A单核苷酸多态性与C反应蛋白（CRP）中位数之间存在显著关联。与具有相同基因型的健康受试者相比，rs9826AA、rs12045886TT和-TC以及rs9017AA基因型的RA患者血清RORc水平更高（分别为p = 0.02、p = 0.04和p = 0.01）。此外，肿胀关节数大于3（p = 0.04）且健康评估问卷（HAQ）评分大于1.5（0.049）的RA患者中，RORc蛋白水平中位数更高。