Distinct Cardiometabolic Profiles for Overweight/Obese People with Different Haptoglobin Phenotypes: A Cross-Sectional Study

Background: Haptoglobin (Hp) is an acute-phase protein crucial for neutralizing oxidative damage and eliminating free hemoglobin. However, the effect of Hp polymorphism on the modulation of anthropometric, metabolic, and inflammatory aspects of obesity remains poorly elucidated. Methods: Hp genotypes, glucometabolic and cardiometabolic markers, serum CD163, and pro-inflammatory and anti-inflammatory markers were assessed in conveniently recruited participants with overweight and obesity of the same racial and ethnic backgrounds. Results: A total of 114 participants (75 males, 39 females; mean age 37.32 ± 11.8 years) with overweight or obesity (BMI = 30.41 ± 5.09 kg/m2) were recruited. Participants with Hp2-1 and Hp2-2 genotypes showed significantly higher (P < 0.05) levels of insulin resistance, total cholesterol, LDL-C, and triglycerides than those with the Hp1-1 genotype. In contrast, participants with the Hp1-1 genotype had substantially higher (P < 0.05) serum Hp levels than those with the Hp2-2 genotype. Furthermore, participants with the Hp2-1 genotype expressed significantly higher (P < 0.05) levels of IL-6 and IL-10 than their counterparts with the Hp2-2 genotype. No significant differences were found in anthropometric measures, IGF-1, insulin sensitivity, HDL-C, CD163, and TNF-α. Conclusion: Hp polymorphism is remarkably associated with distinct metabolic and glucoregulatory aspects in individuals with overweight and obesity, with Hp2-1 and Hp2-2 genotypes associated with higher glucometabolic and cardiometabolic risks. The Hp genotype might serve as a predictive marker for diabetes and cardiovascular diseases. Further research is warranted on the clinical implications of Hp genotyping.