CRP 基因-717 A>G（rs2794521）多态性与系统性红斑狼疮患者 C 反应蛋白高心血管风险的相关性。
Association of - 717 A > G (rs2794521) CRP polymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients.
机构信息
Red de Inmunonutrición Y Genómica Nutricional en Las Enfermedades Autoinmunes, Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, 44340, Guadalajara, Jalisco, Mexico.
Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, 44340, Guadalajara, Jalisco, Mexico.
出版信息
Clin Rheumatol. 2023 Mar;42(3):761-772. doi: 10.1007/s10067-022-06430-6. Epub 2022 Nov 10.
INTRODUCTION
Systemic lupus erythematosus (SLE) is an autoimmune disease where genetic factors have been related to SLE susceptibility and disease severity. CRP polymorphisms have been associated with high C-reactive protein (CRP) serum levels, cardiovascular disease (CVD), and high clinical disease activity in SLE patients; however, the evidence is still inconclusive.
OBJECTIVE
This study was aimed to assess the association of the - 717 A > G, - 409 G > A, + 1444 C > T, and + 1846 C > T CRP polymorphisms with genetic susceptibility, clinical disease activity, and CVD risk in Mexican-mestizo SLE patients.
METHODS
A comparative cross-sectional study was conducted on 369 unrelated women: 183 with SLE according to the 1997 SLE-ACR criteria and 186 healthy subjects (HS). The clinical disease activity was assessed by the Mex-SLEDAI score; CRP and lipid profile were quantified by turbidimetry and colorimetric-enzymatic assays, respectively. The CRP polymorphisms genotyping was carried out by allelic discrimination.
RESULTS
SLE patients with - 717 AA genotype had higher CRP serum levels than SLE carriers of AG and GG genotypes (AA = 5 mg/L vs. AG = 3.2 mg/L vs. GG = 2.4 mg/L; p = 0.01), and the AA genotype was associated with high CVD risk by CRP in SLE patients (OR = 3; CI: 1.2-7.6; p < 0.01).
CONCLUSIONS
The - 717 A > G CRP polymorphism is a risk factor for high CRP levels and high CVD risk in Mexican-mestizo SLE patients. Key Points • Cardiovascular disease is one of the major causes of death in SLE patients due to the higher prevalence of traditional and non-traditional cardiovascular risk factors. • C-reactive protein is a liver-derived acute-phase protein suggested as one powerful independent risk predictor factor for cardiovascular disease. • Single nucleotide polymorphisms in CRP have been suggested as genetic susceptibility factors that could modify the SLE pathophysiology outcomes. • Mexican-mestizo SLE patients carrying the -717 A>G CRP AA genotype had 3-fold high cardiovascular disease risk than SLE patients with AG or GG genotypes.
简介
系统性红斑狼疮（SLE）是一种自身免疫性疾病，遗传因素与 SLE 的易感性和疾病严重程度有关。C 反应蛋白（CRP）多态性与 CRP 血清水平升高、心血管疾病（CVD）和 SLE 患者的高临床疾病活动度有关；然而，证据仍然不确定。
目的
本研究旨在评估 CRP-717A>G、-409G>A、+1444C>T 和+1846C>T 多态性与墨西哥混血 SLE 患者的遗传易感性、临床疾病活动度和 CVD 风险的相关性。
方法
对 369 名无血缘关系的女性进行了一项比较性横断面研究：183 名符合 1997 年 SLE-ACR 标准的 SLE 患者和 186 名健康对照者（HS）。采用 Mex-SLEDAI 评分评估临床疾病活动度；通过比浊法和比色酶法分别定量 CRP 和血脂谱。通过等位基因鉴别进行 CRP 多态性基因分型。
结果
SLE 患者-717AA 基因型的 CRP 血清水平高于 SLE 患者 AG 和 GG 基因型（AA=5mg/L 比 AG=3.2mg/L 比 GG=2.4mg/L；p=0.01），AA 基因型与 SLE 患者高 CRP 水平相关（OR=3；CI：1.2-7.6；p<0.01）。
结论
CRP-717A>G 多态性是墨西哥混血 SLE 患者高 CRP 水平和高 CVD 风险的危险因素。要点•心血管疾病是 SLE 患者死亡的主要原因之一，这是由于传统和非传统心血管危险因素的患病率较高。•C 反应蛋白是一种肝脏来源的急性期蛋白，被认为是心血管疾病的一个强大的独立风险预测因子。•CRP 中的单核苷酸多态性被认为是遗传易感性因素，可以改变 SLE 的病理生理学结果。•与 AG 或 GG 基因型的 SLE 患者相比，携带 CRP-717A>GAA 基因型的墨西哥混血 SLE 患者患心血管疾病的风险高 3 倍。
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