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ORIGINAL RESEARCH article

Front. Med.
Sec. Rheumatology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1442858
This article is part of the Research Topic Cardiovascular Comorbidities in Inflammatory Rheumatic Diseases View all 3 articles

Haptoglobin 2-2 genotype is associated with increased risk of cardiovascular disease in patients with rheumatoid arthritis: a matched case-control study

Provisionally accepted
Chuanhui Xu Chuanhui Xu 1*Lay Wai Khin Lay Wai Khin 2Hui Zhen Tam Hui Zhen Tam 2Liuh Ling Goh Liuh Ling Goh 3Ee Tzun Koh Ee Tzun Koh 1Rinkoo Dalan Rinkoo Dalan 4Khai Pang Leong Khai Pang Leong 1
  • 1 Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore, Singapore
  • 2 Clinical Research & Innovation Office, Tan Tock Seng Hospital, Singapore, Singapore
  • 3 Molecular Diagnostic Laboratory, Tan Tock Seng Hospital, Singapore, Singapore
  • 4 Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore

The final, formatted version of the article will be published soon.

    Traditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). The Haptoglobin (Hp) 2-2 genotype confers a lower anti-oxidant and higher inflammatory effect on the vasculature compared to the non-Hp 2-2 genotype. This study investigates the association of the Hp genotype with CVD in patients with RA.Data from 69 RA patients with CVD and 207 sex-and ethnicity-matched RA patients without CVD, collected from 1 Jan 2000 to 31 Dec 2020, were retrieved from the Tan Tock Seng Hospital RA Registry. CVD was examined against demographics, clinical and laboratory variables in univariate models. Associations between the Hp genotypes and CVD were analyzed using conditional logistic regression.We studied 276 patients (65.2% female, 82.6% Chinese, median age 60.9 years). Most participants were in low disease activity or remission (79.3%). The Hp 2-2 gene was present in 49.6% (137/276). In the group with CVD, the prevalence of the Hp 2-2 genotype was 50.9% (29/57) in the Chinese, 100% (5/5) in the Indians, and 28.6% (2/7) in the Malays. In the non-CVD group, the respective prevalence was 46.8% (80/171), 66.7% (10/15), and 52.4% (11/21).In univariate analysis, the matched odds ratio (OR) of the Hp 2-2 genotype for CVD in RA was 1.34 (95% confidence interval (CI): 1.22-1.47; p < 0.001). The Hp 2-2 genotype was significantly associated with CVD (adjusted matched OR: 1.13; 95% CI: 1.01-1.27; p = 0.033) in the multivariate logistic regression model after adjusting the confounding factors, including age, smoking, diabetes, hypertension, hyperlipidemia, anti-CCP autoantibodies, and disease activity.The Hp 2-2 genotype is associated with an increased risk of CVD in patients with RA in this multi-ethnic cohort.

    Keywords: rheumatoid arthritis, cardiovascular disease, Haptoglobin genotypes, inflammation, personalized medicine Font: Bold Hp: haptoglobin, RA: Rheumatoid Arthritis, OR: odds ratio, 95% CI: 95% confidence interval, CCP: cyclic-citrullinated peptide, DAS-28: disease activity score 28, CVD: cardiovascular disease Font: Italic

    Received: 03 Jun 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Xu, Khin, Tam, Goh, Koh, Dalan and Leong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Chuanhui Xu, Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore, Singapore

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