Haptoglobin 2-2 phenotype is associated with decreased ferroxidase activity in smokers Samir M. Awadallah * Department of Medical Technology, The Hashemite University, P.O. Box 330077, Zarqa 13133, Jordan Received 3 April 2002; received in revised form 14 March 2003; accepted 21 March 2003 Abstract Background: Cigarette smoking and the inheritance of Hp 2-2 phenotype have been separately linked to cardiovascular disease. In this study, the combined effects of smoking and the presence of Hp 2-2 type on predisposition to cardiovascular disease were investigated. Methods: Fasting blood specimens were collected from 489 Jordanian males (228 smokers and 261 nonsmokers). Haptoglobin phenotype was determined by electrophoresis, and lipid profile and ferroxidase activity were determined by spectrophotometric methods. Results: The results show that, irrespective of Hp type, total- and LDL-cholesterol levels were significantly higher in smokers compared with nonsmokers, while levels of HDL-cholesterol and ferroxidase activity were lower in smokers. There was no significant difference between the three Hp types in nonsmokers regarding the lipid profile and ferroxidase activity. In the smokers group, however, serum ferroxidase activity was significantly lower in individuals with Hp 2-2 type compared with that in Hp 1-1 and Hp 2-1 smoker individuals. Smokers with the Hp 2-2 type have significantly higher levels of total- and LDL-cholesterol and lower HDL-cholesterol levels compared with that in nonsmokers expressing the same Hp type. Conclusion: These findings demonstrate that smokers with Hp 2-2 phenotype have a decreased antioxidant capacity suggesting that smoking coupled with the inheritance of an Hp-2-2 type predispose to more oxidative stress and cardiovascular disease. D 2003 Elsevier B.V. All rights reserved. Keywords: Haptoglobin; Smokers; Cardiovascular diseases; Ferroxidase; Lipid profile; Jordan 1. Introduction Haptoglobin is an acute phase reactant protein that binds free hemoglobin in the circulation. Hapto- globin–hemoglobin complex formation prevents both loss of iron and iron-driven oxidative damage [1–3]. Haptoglobin is found in three major pheno- types; Hp 1-1, 2-1 and 2-2, exhibiting distinct structural and functional properties with significant biological and clinical implications [4]. Because of its lower hemoglobin binding ability, lower plasma concentration and poor antioxidant activity, Hp 2-2 phenotype is strongly associated with disorders related to oxidative stress [4–6]. This was supported by the observation that the levels of the antioxidant vitamin C are lower in Hp 2-2 individuals than in individuals with other phenotypes [7], and the find- ing that serum iron, ferritin and transferrin are higher in Hp 2-2 individuals [8]. Additionally, altered serum lipid profile, atherosclerosis, hypertension and cardi- 0009-8981/03/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0009-8981(03)00164-5 * Tel.: +962-5-3826600; fax: +962-5-3826613. E-mail address: sawad@index.com.jo (S.M. Awadallah). www.elsevier.com/locate/clinchim Clinica Chimica Acta 334 (2003) 71 – 76