Haptoglobin 2 allele associates with unstable carotid plaque and major cardiovascular events

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• 作者：Petra Ij?s ; Jani Saksi ; Lauri Soinne ; Jarno Tuimala ; Matti Jauhiainen ; Antti Jula ; Mika K?h?nen ; Y. Antero Kes?niemi ; Petri T. Kovanen ; Markku Kaste ; Perttu J. Lindsberg
• 关键词：Stroke ; Myocardial infarction ; Carotid stenoses ; Intraplaque hemorrhage
• 刊名：Atherosclerosis
• 出版年：2013
• 出版时间：October, 2013
• 年：2013
• 卷：230
• 期：2
• 页码：228-234
• 全文大小：659 K

文摘

Objective

Intraplaque hemorrhages (IPH) may predispose to unstable atherosclerotic disease and its atherothrombotic complications, ischemic stroke and coronary syndromes. However, the discriminative value of IPH has been limited in histological and imaging studies suggesting that confounding factors modulate the response to IPH. We studied whether common variants of haptoglobin (Hp), which facilitates the removal of free hemoglobin and protects tissues from heme-iron induced oxidative damage, would modify the inflammatory response to IPH and the risk of unstable carotid stenosis (CS) and major cardiovascular diseases.

Methods

We genotyped Hp polymorphism in 91 patients with a high-grade CS from Helsinki Carotid Endarterectomy Study (HeCES) and in 1417 individuals from Health 2000, a Finnish epidemiological cross-sectional health survey, and determined heme oxygenase-1 (HO1) expression in relation to Hp genotypes in carotid plaques.

Results

In the Health 2000 cohort, Hp genotype frequencies were 0.143 (hp1-1), 0.486 (hp1-2) and 0.371 (hp2-2) consistent with Hardy-Weinberg equilibrium and those reported from other Caucasian populations. Among patients with unstable CS, the frequency of hp2-2 genotype was higher than in the control population (0.516 vs. 0.371, P?=?0.025). Hp genotypes correlated with HO1 expression in the plaque (r?=?0.47, P?=?0.027). In the Health 2000 cohort, hp2 allele was associated with an increased risk of major cardiovascular diseases (ischemic stroke, TIA, myocardial infarction, coronary heart disease) with an adjusted OR of 1.46 (95 % CI 1.03-2.06).

Conclusion

Common haptoglobin variants modulate the inflammatory response to IPH and associate with the risk of unstable carotid stenosis and major ischemic cardiovascular events.