C-反应蛋白基因多态性影响意大利患者经活检证实的巨细胞动脉炎的易感性和结局。

C-reactive protein gene polymorphisms influence susceptibility and outcomes of biopsy-proven giant cell arteritis in Italian patients.

机构信息

Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Molecular Biology Laboratory, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

出版信息

Clin Exp Rheumatol. 2024 Apr;42(4):803-810. doi: 10.55563/clinexprheumatol/z40y02. Epub 2023 Aug 3.

DOI:10.55563/clinexprheumatol/z40y02

PMID:37534674

Abstract

OBJECTIVES

To investigate potential associations between the two functional C-reactive protein (CRP) gene polymorphisms at position 3872C>T (rs1205) and 4741G>C (rs3093068) and susceptibility, clinical expression, laboratory and pathological findings, and outcomes of giant cell arteritis (GCA) in a Nothern Italian population.

METHODS

One hundred and seventy Italian patients with biopsy-proven GCA resident in Reggio Emilia area, Italy, and 200 healthy controls from the same geographic area were genotyped for rs1205 and rs3093068 CRP gene polymorphisms by molecular methods. The patients were subgrouped on the basis of the presence or absence of clinical manifestations, histological and laboratory findings, and outcomes.

RESULTS

The distribution of rs1205 genotype was significantly different between GCA patients and controls (p=0.018). Homozygosity for T allele was significantly more frequent in GCA patients compared to controls [p=0.006; odds ratio (OR): 2.28 (95% CI: 1.1, 4.8)]. The distribution of rs3093068 genotype differed significantly between GCA patients and controls (p=0.010). Allele C and the carriers of the C allele (C/C+C/G) of rs3093068 genotype were significantly less frequent in GCA patients compared to controls [p=0.002, OR: 0.39 (95% CI: 0.24-0.73); p=0.002, OR: 0.35 (95% CI: 0.17-0.70), respectively]. No significant associations were found between the two polymorphisms and baseline clinical manifestations. The carriers of the allele C of rs3093068 genotype had significantly higher CRP values at diagnosis (13.2±5.0 vs. 8.3±6.0 mg/dl, p=0.007). Homozygosity for T allele of rs1205 genotype had a significantly more frequent eosinophil infiltration of the temporal artery wall (21.4% vs. 6.0%) (p=0.010, OR 4.28;1.31-13.98) than patients carrying the allele C. Carriers of the allele T of rs1205 genotype had lower glucocorticoid (GC) treatment duration (p=0.041), lower cumulative total GC dose (p=0.017), and higher prevalence of long-term remission (p=0.024).

CONCLUSIONS

CRP gene rs1205 and rs3093068 polymorphisms influence GCA susceptibility and its outcomes.

摘要

目的

研究 C 反应蛋白（CRP）基因两个功能位点 3872C>T（rs1205）和 4741G>C（rs3093068）的多态性与巨细胞动脉炎（GCA）易感性、临床表型、实验室和病理发现及结局之间的潜在关联。

方法

采用分子方法，对意大利雷焦艾米利亚地区 170 例经活检证实的 GCA 患者和 200 名来自同一地理区域的健康对照者进行 rs1205 和 rs3093068 CRP 基因多态性的基因分型。根据有无临床表现、组织学和实验室发现以及结局对患者进行亚组分组。

结果

GCA 患者和对照组 rs1205 基因型的分布存在显著差异（p=0.018）。与对照组相比，GCA 患者的 T 等位基因纯合子明显更为常见（p=0.006；比值比[OR]：2.28（95%CI：1.1，4.8]）。GCA 患者和对照组 rs3093068 基因型的分布存在显著差异（p=0.010）。与对照组相比，rs3093068 基因型的 C 等位基因和 C 等位基因携带者（C/C+C/G）明显较少（p=0.002，OR：0.39（95%CI：0.24-0.73）；p=0.002，OR：0.35（95%CI：0.17-0.70））。这两种多态性与基线临床表型之间未发现明显相关性。rs3093068 基因型 C 等位基因携带者的 CRP 值在诊断时明显更高（13.2±5.0 与 8.3±6.0 mg/dl，p=0.007）。rs1205 基因型 T 等位基因纯合子的颞动脉壁嗜酸性粒细胞浸润更为常见（21.4%与 6.0%）（p=0.010，OR 4.28；1.31-13.98）。rs1205 基因型 T 等位基因携带者的糖皮质激素（GC）治疗时间更短（p=0.041）、总 GC 剂量累积量更低（p=0.017）和长期缓解的患病率更高（p=0.024）。