Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study

Emily Kate Mewborn; Elizabeth Ann Tolley; David Bruce Wright; Amy Lynn Doneen; Margaret Harvey; Ansley Grimes Stanfill

doi:10.1016/j.ajpc.2023.100625

Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study

Am J Prev Cardiol. 2023 Dec 10:17:100625. doi: 10.1016/j.ajpc.2023.100625. eCollection 2024 Mar.

Authors

Emily Kate Mewborn¹, Elizabeth Ann Tolley², David Bruce Wright³, Amy Lynn Doneen⁴, Margaret Harvey⁵, Ansley Grimes Stanfill^{5

6}

Affiliations

¹ University of Tennessee Health Science Center, 874 Union Avenue, Suite G022B, Memphis, TN 38163, United States.
² Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States.
³ Premier Prevention, Memphis, TN, United States.
⁴ The Prevention Center for Heart & Brain Health, Spokane, WA, United States.
⁵ Department of Acute and Tertiary Care, College of Nursing, University of Tennessee Health Science Center, Memphis, TN, United States.
⁶ Department of Genetics, Genomics, and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States.

Abstract

Objective: Coronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes.

Methods: The researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35-70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression.

Results: The sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01).

Conclusion: Haptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

Keywords: Atherosclerosis; Haptoglobin genotype; Oxidative stress; Prediabetes.