Atherosclerosis in patients infected with HIV is influenced by a mutant monocyte chemoattractant protein-1 allele.
ABSTRACT 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.
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).
HIV-infected patients with the MCP-1-2518G allele have a 5-fold increased risk for atherosclerosis, as assessed by ultrasonography.
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ABSTRACT: Monocyte chemoattractant proteins (MCPs) are important cytokines that involved in cellular activation and releasing of inflammatoy mediators by basophils and eosinophils in allergic disease. Some MCP gene variants implicate in asthma and monoclonal antibody for MCP-3 blocks allergic inflammations in the patients with asthma. Detection of interactions between gene and environment or between genes for complex disease such as asthma is important. We searched for an evidence of genetic effect of single nucleotide polymorphisms (SNPs) of MCP genes as well as gene - gene interactions involved in asthma.Allergy, asthma & immunology research 07/2014; 6(4):333-40. DOI:10.4168/aair.2014.6.4.333 · 3.08 Impact Factor
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ABSTRACT: HIV-infected patients are known to be at risk for premature coronary artery disease. This emerging paradigm is a rising concern for clinicians. Due to advances in the treatment of HIV, this once fatal infection has been transformed into a chronic illness. Traditional risk factors paired with the long-term use of antiretroviral therapy (ART) and chronic inflammation leads to premature atherosclerosis, particularly progression of atherosclerotic plaque. This population of patients requires early recognition of subclinical atherosclerosis, as well aggressive primary and secondary prevention strategies among the multi-disciplinary team of physicians caring for them. We sought to present a comprehensive review of the available literature related to HIV and atherosclerosis and cardiovascular risk.American Journal of Cardiovascular Drugs 02/2015; DOI:10.1007/s40256-015-0105-8 · 2.20 Impact Factor
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ABSTRACT: Aims: We present a genetic association study in 106 European HIV-infected individuals aimed at identifying and confirming polymorphisms that have a significant influence on toxicity derived from treatment with lopinavir/ritonavir (LPV/r). Patients & methods: Genotyping was performed by matrix-assisted laser desorption/ionization-time of flight and KASPar® (KBiosciences, Hoddesdon, UK); LPV/r plasma concentrations were quantified using HPLC with an UV detection system and the pharmacokinetic parameters were estimated using Bayesian algorithms. Genetic association analysis was performed with PASW Statistics 18 (SPSS Inc., IL, USA) and R for Windows (Microsoft, WA, USA). Results: Suggestive relationships have been established between lipid plasma levels and total bilirubin and SNPs in CETP, MCP1, ABCC2, LEP and SLCO1B3 genes and between diarrhea and SNPs in IL6 gene. Conclusion: Replication analysis should confirm the novel results obtained in this study prior to its application in the clinical practice to achieve a safer LPV/r-based combined antiretroviral therapy.Personalized Medicine 05/2014; 11(3):263-272. DOI:10.2217/pme.14.7 · 1.13 Impact Factor