Association of − 717 A > G (rs2794521) CRP polymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients

• Published in: Clinical rheumatology 2023-03, Vol.42 (3), p.761-772
• Main Authors: Pesqueda-Cendejas, Karen, Parra-Rojas, Isela, Meza-Meza, Mónica R., Mora-García, Paulina E., Campos-López, Bertha, Ruiz-Ballesteros, Adolfo I., Montoya-Buelna, Margarita, Rivera-Escoto, Melissa, Moreno-Ortiz, José M., Bautista-Herrera, Luis A., Cerpa-Cruz, Sergio, De la Cruz-Mosso, Ulises
• Format: Article
• Language: English
• Subjects: Acute phase proteins; Autoimmune diseases; C-reactive protein; C-Reactive Protein - metabolism; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - etiology; Case-Control Studies; Colorimetry; Cross-Sectional Studies; Female; Gene Frequency; Gene polymorphism; Genetic factors; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Genotyping; Heart Disease Risk Factors; Humans; Lupus; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - genetics; Medicine; Medicine & Public Health; Original Article; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Rheumatology; Risk Factors; Serum levels; Single-nucleotide polymorphism; Susceptibility; Systemic lupus erythematosus
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-022-06430-6

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   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