Haptoglobin 1 gene polymorphism protects against postoperative cardiovascular events

Abstract

Abstract Background Haptoglobin (Hp) is a plasma glycoprotein with antioxidant properties that plays a role in maintaining the integrity of the bloodstream and in clearing plasma lipids. The human haptoglobin gene is polymorphic, with two prevalent alleles (Hp1 and Hp2) resulting in three distinct phenotypes. The Hp subtypes have been linked to the risk of symptomatic carotid stenosis and major ischemic cardiovascular events, with some studies suggesting a protective role of the Hp1 allele. However, observed discrepancies in the relationship between Hp genotype and cardiovascular events suggest the presence of additional underlying mechanisms or differences among Hp1 allele subtypes. This study aims to examine the role of Hp1 alleles (Hp1F and Hp1S) in atherosclerosis and determine their association with cardiovascular events in our cohort of carotid endarterectomy patients. Methods The study included a total of 691 patients who underwent a carotid endarterectomy. All patients underwent genotyping for Haptoglobin. A total of 668 carotid plaques were collected, and 45 of these plaques were randomly selected for histopathological analysis and underwent staining for lipids using (Oil Red O), hemorrhage (glycophorin A), macrophages (CD68 [cluster of differentiation 68]), smooth muscle cells (alpha-actin) and collagen (Movat pentachrome). Participants were subsequently followed-up for postoperative cardiovascular events using data from clinical registers. The median follow-up for cardiovascular events was 48 months. All included patients gave written informed consent. The study was approved by the local ethical review board and followed the declaration of Helsinki. Results There were no significant differences in the baseline clinical characteristics between Hp1S carriers (36.6%) and non-carriers (63.4%). Postoperative cardiovascular and mortality events were found to be significantly associated with Hp1S subtype, with carriers exhibiting a decreased risk (HR=0.372, 95%CI 0.180-0.769, p=0.008). The histological examination of the plaques revealed that Hp1S carriers had a significantly greater percentage of plaque area stained positive alpha-actin (p=0.033). However, there were no significant differences observed in other histological markers. Conclusions Hp1S was associated with lower risk of postoperative cardiovascular events in our cohort of carotid endarterectomy patients. Patients with this genotype had plaques with more smooth muscle cells, so possibly more stable. This suggests that Hp1 subtypes could be of interest in risk stratification of this patient population, deserving further studies.