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10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV6-8 November 2008, London, UK |
ß2-ADRENERGIC RECEPTOR POLYMORPHISMS ARE LINKED TO LIPOACCUMULATION WHILE A ß3-ADRENERGIC RECEPTOR POLYMORPHISM INFLUENCES LIPOATROPHY
Antiviral Therapy 2008; 13(Suppl. 4):A12 (abstract no. O-16)
A Riva1, M Nasi2, BZ Poma1, P Cicconi3, S Martone1, AD Monforte3, A Cossarizza2 and M Galli1
1Department of Clinical Sciences, Section of Infectious Diseases and Tropical Medicine, “Luigi Sacco” Hospital, University of Milan, Milan, Italy; 2Department of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia, Modena, Italy; 3Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, “San Paolo” Hospital - University of Milan, Milan, Italy
OBJECTIVES: Adrenergic receptors (AR) are essential components of the autonomic nervous system, which controls various physiological functions including metabolism of glucose and lipids. An association has been suggested betweeen obesity phenotypes and some polymorphisms located in the functional regions of the ß3- and the ß2-AR. The aim of our study was the evaluation of the role of ß3- and ß2-AR polymorphisms in the onset of lipodystrophy in patients of the Italian Cohort of Antiretroviral-Naïve patients (I.Co.Na).
METHODS: We randomly selected for this study 255 patients included in LipoICoNa after excluding non-Caucasian patients. For the identification of the polymorphisms, we used a sequence selective hybridization followed by a sequence-dependent termination and a sequence-specific primer extension. A standard Poisson regression multivariable model was used to study whether the polymorphisms were predictors of lipoatrophy and fat accumulation.
RESULTS: In a follow-up of 973 person-years, 70 patients developed lipoatrophy, 7.1 per 100 person-years of follow-up (PYFU; 95% confidence interval [CI] 5.6–9.1). ß3-AR codon 64 TT genotype carriers tended to be at lower risk of lypoatrophy as compared with those with a TC/TT genotype (adjusted relative risk [ARR] 0.39, 95% CI 0.14–1.06 versus TC/CC, P=0.066). In a follow-up of 976 person-years, 63 patients developed at least one pathological characteristic typical of fat accumulation (IR 6.45, 95% CI 5.04–8.26 per 100 PYFU). The ß2-AR codon 16 AA genotype was significantly associated with higher risk (ARR 3.72, 95% CI 1.58–8.76 versus AG/ GG, P=0.0026), whereas the ß2-AR codon 27 CC genotype was significantly associated with lower risk (ARR 0.21, 95% CI 0.08–0.51 versus CG/GG, P=0.0006).
DISCUSSION: The ADRß3 protein is a G-coupled receptor expressed on adipocytes involved in lipolysis. The C mutation might determine a reduced function of the receptor and inhibit triglycerides accumulation in adipocytes favouring lipoatrophy. The ß2-AR is the main lipolytic receptor in white human adipose tissue. The glutamic acid 27 allele is a risk factor for the accumulation of visceral fat. Our data supports the involvement of codon 27 CG/CC and codon 16 AA genotypes in fat accumulation and underlines the potential risk of long term cardiovascular disease in HIV-1-infected patients receiving antiretroviral therapy. Given the high prevalence of the polymorphism analysed and the relative low cost and feasibility of gene testing, it might be useful to determine the genetic predisposition of each single HIV-1-positive patient starting antiretroviral therapy. It could be possible to design individual regimens for each patient in order to avoid the rapid emergence of side effects and take adequate measures to delay their appearance.
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2008-11-06
O-16
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