中国汉族人群中 RIPK1 和 RIPK2 基因多态性与类风湿关节炎的关系

IF 2.6 Q2 GENETICS & HEREDITY
Application of Clinical Genetics Pub Date : 2024-10-19 eCollection Date: 2024-01-01 DOI:10.2147/TACG.S472418
Shuang Lv, Yiming Li, Bojian Sun, Yu Jing, Xing Wang, Zhanqing Gu, Bailiang Wang, Cheng Xiao
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引用次数: 0

摘要

对象:类风湿性关节炎(RA)是一种系统性自身免疫性疾病,其发病机制尚不明确。本研究旨在确定特定单核苷酸多态性(SNPs)(即 RIPK1 基因中的 rs17548629 和 RIPK2 基因中的 rs10094579)对 RA 的易感性。此外,该研究还探讨了疾病不同阶段炎症标记物与生化指标之间的关联:我们分析了 394 名 RA 患者和 258 名正常对照(NCs),使用聚合酶链式反应(PCR)和测序技术检测了 RIPK1(rs17548629)和 RIPK2(rs10094579)基因中的 SNPs。对 RA 患者的炎症指标(包括 C 反应蛋白 (CRP) 和红细胞沉降率 (ESR))以及生化指标(如丙氨酸氨基转移酶 (ALT)、天门冬氨酸氨基转移酶 (AST)、尿素、葡萄糖、尿酸和肌酐)进行了评估。此外,疾病特异性指标还包括环瓜氨酸肽(CCP)、类风湿因子(RF)、抗核抗体(ANA)和抗角蛋白抗体。以血沉为基础的疾病活动度评分28(DAS28)将RA患者分为高、中、低疾病活动度组:我们发现,RIPK1 rs17548629基因型与RA在加性模型(p < 0.001; OR = 3.23)、超显性模型(p < 0.001; OR = 0.27)和显性模型(p < 0.001; OR = 3.94)中均有明显相关性。在NCs患者中,rs17548629的C等位基因频率明显高于RA患者(p < 0.001; OR = 0.322)。与正常对照组相比,RIPK1 rs17548629基因型与抗CCP阳性的RA患者(p < 0.001)和抗CCP阴性的RA患者(p < 0.001)均有显著相关性。同样,该基因型也与 RF 阳性的 RA 患者有关(p < 0.001)。此外,在超显性模型中,RIPK2 rs10094579基因型与疾病活动度低的RA患者的CRP水平显著相关(p = 0.029; OR = 0.065,根据年龄和性别调整):结论:在加性、共显性和显性模型中,RIPK1 rs17548629 基因型的存在与 RA 相关。在中国人群中,rs17548629的T等位基因突变会增加罹患RA的风险。经鉴定,RIPK1 rs17548629基因型与RF阳性的RA患者有关,而在RF阴性的个体中未观察到明显的相关性。这些研究结果表明,该 SNP 可能以依赖射频的方式调节 RA 的患病风险。此外,RIPK2 rs10094579 基因型与表现出低疾病活动性的 RA 患者的 CRP 水平相关。这种关联强调,对于携带 RIPK2 rs10094579 CA 基因型的低疾病活动性 RA 患者,在减少治疗剂量时必须谨慎。我们有必要开展更多研究,探索可能影响 RA 易感性的其他基因型,并完善潜在的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.

Objects: Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease.

Methods: We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity.

Results: We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (p < 0.001; OR = 3.23), over-dominant model (p < 0.001; OR = 0.27), and dominant model (p < 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (p < 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (p < 0.001) and anti-CCP-negative RA patients (p < 0.001). Similarly, this genotype was associated with RF-positive RA patients (p < 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (p = 0.029; OR = 0.065, adjusted for age and sex).

Conclusion: The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094579. Additional research is warranted to explore other genotypes that may influence RA susceptibility and to refine potential treatment strategies.

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来源期刊
Application of Clinical Genetics
Application of Clinical Genetics Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
5.40
自引率
0.00%
发文量
20
审稿时长
16 weeks
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