L Egaña-Gorroño1, E Martínez2, I Pérez2, T Escribà1, P Domingo3, J M Gatell4, M Arnedo5. 1. Group of Genomics and Pharmacogenomics, Retrovirology and Viral Immunopathology Laboratory, IDIBAPS, Barcelona, Spain. 2. Department of Infectious Diseases, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain. 3. Department of Infectious Diseases, Hospital de Sant Pau, Barcelona, Spain. 4. Group of Genomics and Pharmacogenomics, Retrovirology and Viral Immunopathology Laboratory, IDIBAPS, Barcelona, Spain Department of Infectious Diseases, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain. 5. Group of Genomics and Pharmacogenomics, Retrovirology and Viral Immunopathology Laboratory, IDIBAPS, Barcelona, Spain marnedo@clinic.ub.es.
Abstract
OBJECTIVES: To evaluate the association of host genetics with changes in limb or trunk fat in a group of antiretroviral therapy (ART)-naive HIV-infected patients prospectively followed up according to the initiation and the type of ART. METHODS: Fifty single nucleotide polymorphisms (SNPs) in 26 genes, associated with obesity, insulin resistance, lipid metabolism or lipodystrophy in previously published genetic studies, were assessed in ART-naive HIV-infected Caucasian patients divided into three groups: 24 (27%) did not start ART, 29 (32.6%) received zidovudine or stavudine and 36 (40.4%) received neither zidovudine nor stavudine in their initial regimen. Patients underwent body fat measurements (using dual-energy X-ray absorptiometry) at baseline and Month 12. A multivariate model using backward stepwise elimination was used to assess the influence of SNPs and baseline levels of non-genetic covariates on changes in limb or trunk fat. RESULTS: The baseline characteristics were: 73% men, 17% coinfected with hepatitis C virus and/or hepatitis B virus, median age 37 years, median CD4+ T cell count 228/mm(3), median HIV-RNA 5.2 log copies/mL, median plasma glucose 85 mg/dL, median plasma insulin 9.1 IU/mL, median limb fat 5.6 kg and median trunk fat 7.0 kg. There were no baseline differences among the three groups except for the CD4+ T cell count. The decrease in limb fat was greater in the no-ART group relative to the other two groups (P < 0.05). The multivariate model showed associations of rs1801278 in IRS1 (P = 0.029, OR = 0.13), baseline viral load (P = 0.006; OR = 4.453) and baseline glucose levels (P = 0.008, OR = 0.926) with loss of limb fat, and rs2228671 in LDLR (P = 0.012, OR = 0.108), rs405509 in APOE (P = 0.048, OR = 0.205), baseline viral load (P = 0.005, OR = 0.186) and baseline CD4+ T cell count (P = 0.01, OR = 1.008) with gain of trunk fat. CONCLUSIONS: Specific polymorphisms in IRS1 (limb fat loss) and LDLR and APOE (trunk fat gain) were identified as independent markers of fat changes irrespective of the initiation of ART and the type of ART and deserve further validation.
OBJECTIVES: To evaluate the association of host genetics with changes in limb or trunk fat in a group of antiretroviral therapy (ART)-naive HIV-infectedpatients prospectively followed up according to the initiation and the type of ART. METHODS: Fifty single nucleotide polymorphisms (SNPs) in 26 genes, associated with obesity, insulin resistance, lipid metabolism or lipodystrophy in previously published genetic studies, were assessed in ART-naive HIV-infected Caucasian patients divided into three groups: 24 (27%) did not start ART, 29 (32.6%) received zidovudine or stavudine and 36 (40.4%) received neither zidovudine nor stavudine in their initial regimen. Patients underwent body fat measurements (using dual-energy X-ray absorptiometry) at baseline and Month 12. A multivariate model using backward stepwise elimination was used to assess the influence of SNPs and baseline levels of non-genetic covariates on changes in limb or trunk fat. RESULTS: The baseline characteristics were: 73% men, 17% coinfected with hepatitis C virus and/or hepatitis B virus, median age 37 years, median CD4+ T cell count 228/mm(3), median HIV-RNA 5.2 log copies/mL, median plasma glucose 85 mg/dL, median plasma insulin 9.1 IU/mL, median limb fat 5.6 kg and median trunk fat 7.0 kg. There were no baseline differences among the three groups except for the CD4+ T cell count. The decrease in limb fat was greater in the no-ART group relative to the other two groups (P < 0.05). The multivariate model showed associations of rs1801278 in IRS1 (P = 0.029, OR = 0.13), baseline viral load (P = 0.006; OR = 4.453) and baseline glucose levels (P = 0.008, OR = 0.926) with loss of limb fat, and rs2228671 in LDLR (P = 0.012, OR = 0.108), rs405509 in APOE (P = 0.048, OR = 0.205), baseline viral load (P = 0.005, OR = 0.186) and baseline CD4+ T cell count (P = 0.01, OR = 1.008) with gain of trunk fat. CONCLUSIONS: Specific polymorphisms in IRS1 (limb fat loss) and LDLR and APOE (trunk fat gain) were identified as independent markers of fat changes irrespective of the initiation of ART and the type of ART and deserve further validation.
Authors: Catalina Barceló; Monia Guidi; Christian W Thorball; Christian Hammer; Aziz Chaouch; Alexandra U Scherrer; Barbara Hasse; Matthias Cavassini; Hansjakob Furrer; Alexandra Calmy; Sebastian Haubitz; Enos Bernasconi; Thierry Buclin; Jacques Fellay; Philip E Tarr; Chantal Csajka Journal: Open Forum Infect Dis Date: 2020-01-22 Impact factor: 4.423
Authors: Elena Bresciani; Nicola Squillace; Valentina Orsini; Roberta Piolini; Laura Rizzi; Laura Molteni; Ramona Meanti; Alessandro Soria; Giuseppe Lapadula; Alessandra Bandera; Andrea Gori; Paolo Bonfanti; Robert John Omeljaniuk; Vittorio Locatelli; Antonio Torsello Journal: Int J Mol Sci Date: 2022-03-23 Impact factor: 5.923