Published Online
on October 4, 2004

A more recent version of this article appeared on October 12, 2004

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Submitted on November 6, 2003
Revised on May 13, 2004
Accepted on May 25, 2004

Atherosclerosis in Patients Infected With HIV Is Influenced by a Mutant Monocyte Chemoattractant Protein-1 Allele

Carlos Alonso-Villaverde MD^*, Blai Coll MD, Sandra Parra MD, Manuel Montero MD, Nahum Calvo MD, Mònica Tous PhD, Jorge Joven MD, and Lluis Masana MD

From the Servei de Medicina Interna (C.A.-V., S.P., L.M.), Institut de Recerca en Ciències de la Salut (B.C.), Servei de Radiologia (M.M., N.C.), and Centre de Recerca Biomèdica (M.T., J.J.) of the Hospital Universitari de Sant Joan, Reus, Spain.

^* To whom correspondence should be addressed. E-mail: cavillaverde\{at}grupsagessa.com.

Background--Patients infected with HIV present with premature atherosclerosis, and the 2 diseases share common pathogenic pathways. We investigated mutations in the monocyte chemoattractant protein-1 (MCP-1) and CCR-2 genes, which are known to control aspects of these pathways, to ascertain whether they are involved in atherogenesis in these patients.

Methods and Results--We performed carotid and femoral artery ultrasonography to detect subclinical atherosclerosis in patients infected with HIV (n=183). MCP-1-2518G and CCR-2 64I polymorphisms were determined in the HIV group and in a population-based control group (n=348). We also determined MCP-1 circulating levels in the HIV group. The presence of MCP-1-2518G in the group of patients with subclinical atherosclerosis was significantly higher than in patients without atherosclerotic lesions (47.5% versus 18.2%, respectively; P<0.001). Furthermore, the patients with atherosclerotic lesions had higher MCP-1 plasma concentrations than did patients without lesions (74.15 [4.03] versus 57.81 [3.67] pg/mL, respectively; P=0.03). When adjusted for known cardiovascular risk factors, the MCP-1-2518G allele was associated with subclinical atherosclerosis (OR 5.72, 95% CI 1.74 to 18.80, P=0.004). Compared with measurements conducted 2.5 years earlier in a subset of 40 patients, intima-media thickness (IMT) in the carotid artery progressed at a mean rate of 0.06 mm/y more rapidly in patients bearing the MCP-1-mutated allele (P=0.08).

Conclusions--HIV-infected patients with the MCP-1-2518G allele have a 5-fold increased risk for atherosclerosis, as assessed by ultrasonography.

Key words: atherosclerosis • HIV • inflammation • genotype • prevention

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