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

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Abstract

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

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Data availability

Data used to support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We acknowledge the clinical and logistic support for the recruitment of the SLE patients given by the Rheumatologists from the Departamento de Reumatología, O.P.D. Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico.

Funding

This study was supported by Grant Programa de Apoyo a la Mejora en las Condiciones de Producción de los Miembros del SNI y SNCA 2019–2021 from the University of Guadalajara for Ulises de la Cruz-Mosso, PhD (U.D.C.M.).

Author information

Authors and Affiliations

  1. Red de Inmunonutrición Y Genómica Nutricional en Las Enfermedades Autoinmunes, Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, 44340, Guadalajara, Jalisco, Mexico

    Karen Pesqueda-Cendejas, Isela Parra-Rojas, Mónica R. Meza-Meza, Paulina E. Mora-García, Bertha Campos-López, Adolfo I. Ruiz-Ballesteros, Margarita Montoya-Buelna, Melissa Rivera-Escoto & Ulises De la Cruz-Mosso

  2. Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, 44340, Guadalajara, Jalisco, Mexico

    Karen Pesqueda-Cendejas, Mónica R. Meza-Meza, Paulina E. Mora-García, Bertha Campos-López, Adolfo I. Ruiz-Ballesteros, Melissa Rivera-Escoto & Ulises De la Cruz-Mosso

  3. Laboratorio de Investigación en Obesidad Y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, 39087, Chilpancingo de los Bravo, Guerrero, Mexico

    Isela Parra-Rojas

  4. Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, 44340, Guadalajara, Jalisco, Mexico

    Margarita Montoya-Buelna

  5. Instituto de Genética Humana “Dr. Enrique Corona Rivera, Departamento de Biología Molecular Y Genómica, Centro Universitario de Ciencias de La Salud, Universidad de Guadalajara, 44340, Guadalajara, Jalisco, Mexico

    José M. Moreno-Ortiz

  6. Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas E Ingenierías, Universidad de Guadalajara, 44430, Guadalajara, Jalisco, Mexico

    Luis A. Bautista-Herrera

  7. Departamento de Reumatología, O.P.D. Hospital Civil de Guadalajara Fray Antonio Alcalde, 44280, Guadalajara, Jalisco, Mexico

    Sergio Cerpa-Cruz

Authors
  1. Karen Pesqueda-Cendejas
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  2. Isela Parra-Rojas
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  3. Mónica R. Meza-Meza
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  5. Bertha Campos-López
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  12. Ulises De la Cruz-Mosso
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Contributions

Conceptualization: UDCM; data curation: PEMG, AIRB, MRMM, BCL, and MRE; formal analysis: KPC, IPR, MMB, AIRB, MRMM, BCL, MRE, LABH, JMMO, SCC, and UDCM; funding acquisition: UDCM; investigation: KPC, PEMG, AIRB, MRMM, BCL, MRE, and SCC; methodology: IPR, MMB, and UDCM; project administration: UDCM; writing—original draft: KPC and UDCM; writing—review and editing: KPC, IPR, PMG, MMB, JMMO, SCC, and UDCM.

Corresponding author

Correspondence to Ulises De la Cruz-Mosso.

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Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Research Ethical Committee of the University of Guadalajara (CI-05018 CUCS-UdeG), based on national and international ethical guidelines. Before enrollment in the study, all SLE patients and HS provided written informed consent according to the ethical guidelines.

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Pesqueda-Cendejas, K., Parra-Rojas, I., Meza-Meza, M.R. et al. Association of − 717 A > G (rs2794521) CRP polymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients. Clin Rheumatol 42, 761–772 (2023). https://doi.org/10.1007/s10067-022-06430-6

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