Atherosclerosis in patients infected with HIV is influenced by a mutant monocyte chemoattractant protein-1 allele.
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.


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 approximately 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.
Alonso-Villaverde
Carlos
C
Servei de Medicina Interna, Hospital Universitari de Sant Joan, 43201 Reus, Spain. cavillaverde@grupsagessa.com
Coll
Blai
B
Parra
Sandra
S
Montero
Manuel
M
Calvo
Nahum
N
Tous
Mònica
M
Joven
Jorge
J
Masana
Lluis
L
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D002097:C-Reactive Protein / Q000032:analysis; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D002097:C-Reactive Protein