OBJECTIVES: To investigate the role of genetic variation in influencing the risk of metabolic complications associated with highly active antiretroviral therapy (HAART). METHODS: Cluster analysis of metabolic traits of 189 patients enrolled in ACTG5005s, the metabolic substudy of ACTG384, a clinical trial of HAART, was performed to identify a subgroup of individuals with increased risk of developing a cluster of metabolic abnormalities after exposure to HAART. Almost 300 single nucleotide polymorphisms in 135 candidate genes were evaluated for their association with this subgroup. RESULTS: A subgroup of patients was identified that had a normal metabolic profile at baseline but developed significantly elevated lipids and insulin resistance on HAART. This high-risk subgroup of patients also experienced significant body composition changes, particularly limb fat loss. Candidate gene analysis revealed that a single nucleotide polymorphism in resistin, a gene previously implicated in obesity and insulin resistance, was associated with this high-risk group (P = 0.0003). CONCLUSION: Genetic variation in resistin is associated with metabolic complications caused by HAART.
OBJECTIVES: To investigate the role of genetic variation in influencing the risk of metabolic complications associated with highly active antiretroviral therapy (HAART). METHODS: Cluster analysis of metabolic traits of 189 patients enrolled in ACTG5005s, the metabolic substudy of ACTG384, a clinical trial of HAART, was performed to identify a subgroup of individuals with increased risk of developing a cluster of metabolic abnormalities after exposure to HAART. Almost 300 single nucleotide polymorphisms in 135 candidate genes were evaluated for their association with this subgroup. RESULTS: A subgroup of patients was identified that had a normal metabolic profile at baseline but developed significantly elevated lipids and insulin resistance on HAART. This high-risk subgroup of patients also experienced significant body composition changes, particularly limb fat loss. Candidate gene analysis revealed that a single nucleotide polymorphism in resistin, a gene previously implicated in obesity and insulin resistance, was associated with this high-risk group (P = 0.0003). CONCLUSION: Genetic variation in resistin is associated with metabolic complications caused by HAART.
Authors: Struan F A Grant; Gudmar Thorleifsson; Inga Reynisdottir; Rafn Benediktsson; Andrei Manolescu; Jesus Sainz; Agnar Helgason; Hreinn Stefansson; Valur Emilsson; Anna Helgadottir; Unnur Styrkarsdottir; Kristinn P Magnusson; G Bragi Walters; Ebba Palsdottir; Thorbjorg Jonsdottir; Thorunn Gudmundsdottir; Arnaldur Gylfason; Jona Saemundsdottir; Robert L Wilensky; Muredach P Reilly; Daniel J Rader; Yu Bagger; Claus Christiansen; Vilmundur Gudnason; Gunnar Sigurdsson; Unnur Thorsteinsdottir; Jeffrey R Gulcher; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2006-01-15 Impact factor: 38.330
Authors: C M Perou; T Sørlie; M B Eisen; M van de Rijn; S S Jeffrey; C A Rees; J R Pollack; D T Ross; H Johnsen; L A Akslen; O Fluge; A Pergamenschikov; C Williams; S X Zhu; P E Lønning; A L Børresen-Dale; P O Brown; D Botstein Journal: Nature Date: 2000-08-17 Impact factor: 49.962
Authors: Michael P Dubé; Robert A Parker; Pablo Tebas; Steven K Grinspoon; Robert A Zackin; Gregory K Robbins; Ronenn Roubenoff; Robert W Shafer; David A Wininger; William A Meyer; Sally W Snyder; Kathleen Mulligan Journal: AIDS Date: 2005-11-04 Impact factor: 4.177
Authors: Gregory K Robbins; Victor De Gruttola; Robert W Shafer; Laura M Smeaton; Sally W Snyder; Carla Pettinelli; Michael P Dubé; Margaret A Fischl; Richard B Pollard; Robert Delapenha; Linda Gedeon; Charles van der Horst; Robert L Murphy; Mark I Becker; Richard T D'Aquila; Stefano Vella; Thomas C Merigan; Martin S Hirsch Journal: N Engl J Med Date: 2003-12-11 Impact factor: 91.245
Authors: Michael Lehrke; Muredach P Reilly; Segan C Millington; Nayyar Iqbal; Daniel J Rader; Mitchell A Lazar Journal: PLoS Med Date: 2004-11-30 Impact factor: 11.069
Authors: Todd Hulgan; Richard Haubrich; Sharon A Riddler; Pablo Tebas; Marylyn D Ritchie; Grace A McComsey; David W Haas; Jeffrey A Canter Journal: AIDS Date: 2011-01-02 Impact factor: 4.177
Authors: Marguerite Ryan Irvin; Sadeep Shrestha; Yii-Der I Chen; Howard W Wiener; Talin Haritunians; Laura K Vaughan; Hemant K Tiwari; Kent D Taylor; Rebecca Scherzer; Michael S Saag; Carl Grunfeld; Jerome I Rotter; Donna K Arnett Journal: Pharmacogenet Genomics Date: 2011-12 Impact factor: 2.089
Authors: Shilpa H Jain; Joseph M Massaro; Udo Hoffmann; Guido A Rosito; Ramachandran S Vasan; Annaswamy Raji; Christopher J O'Donnell; James B Meigs; Caroline S Fox Journal: Diabetes Care Date: 2009-02-17 Impact factor: 19.112