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Impact of Single Nucleotide Polymorphisms and of Clinical Risk Factors on New-Onset Diabetes Mellitus in HIV-Infected Individuals

Rotger, Margalida ; Gsponer, Thomas ; Martinez, Raquel ; Taffé, Patrick ; Elzi, Luigia ; Vernazza, Pietro ; Cavassini, Matthias ; Bernasconi, Enos ; Hirschel, Bernard ; Furrer, Hansjakob ; Weber, Rainer ; Ledergerber, Bruno ; Egger, Matthias ; Telenti, Amalio ; Tarr, Philip E.

In: Clinical Infectious Diseases, 2010, vol. 51, no. 9, p. 1090-1098

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    Title
    • Impact of Single Nucleotide Polymorphisms and of Clinical Risk Factors on New-Onset Diabetes Mellitus in HIV-Infected Individuals
    Author
    • Rotger, Margalida. Institute of Microbiology, University Hospital and University of Lausanne
    • Gsponer, Thomas. Institute for Social and Preventive Medicine, University of Bern
    • Martinez, Raquel. Institute of Microbiology, University Hospital and University of Lausanne
    • Taffé, Patrick. Swiss HIV Cohort Study Data Center
    • Elzi, Luigia. Infectious Diseases Service, University Hospital
    • Vernazza, Pietro. Kantonsspital St. Gallen, St. Gallen
    • Cavassini, Matthias. Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne
    • Bernasconi, Enos. Ospedale Regionale, Lugano
    • Hirschel, Bernard. University Hospital, Geneva
    • Furrer, Hansjakob. Clinic for Infectious Diseases, Bern University Hospital and University of Bern, Bern
    • Weber, Rainer. University Hospital Zurich, University of Zurich, Zurich, Switzerland
    • Ledergerber, Bruno. University Hospital Zurich, University of Zurich, Zurich, Switzerland
    • Egger, Matthias. Institute for Social and Preventive Medicine, University of Bern
    • Telenti, Amalio. Institute of Microbiology, University Hospital and University of Lausanne
    • Tarr, Philip E.. Kantonsspital Bruderholz, University of Basel, Basel
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Clinical Infectious Diseases, 2010, vol. 51, no. 9, p. 1090-1098. The University of Chicago Press
    Other Version
    Classification
    • Health
    OAI-PMH Identifier
    • oai:doc.rero.ch:300012
    Summary
    Background.Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficienc virus (HIV)-infected individuals. Recent genome-wide association studies have reliably associated multiple single nucleotide polymorphisms (SNPs) to DM in the general population. Methods.We evaluated the contribution of 22 SNPs identifie in genome-wide association studies and of longitudinally measured clinical factors to DM. We genotyped all 94 white participants in the Swiss HIV Cohort Study who developed DM from 1 January 1999 through 31 August 2009 and 550 participants without DM. Analyses were based on 6054 person-years of follow-up and 13,922 measurements of plasma glucose. Results.The contribution to DM risk explained by SNPs (14% of DM variability) was larger than the contribution to DM risk explained by current or cumulative exposure to different antiretroviral therapy combinations (3% of DM variability). Participants with the most unfavorable genetic score (representing 12% and 19% of the study population, respectively, when applying 2 different genetic scores) had incidence rate ratios for DM of 3.80 (95% confidenc interval [CI], 2.05-7.06) and 2.74 (95% CI, 1.53-4.88), respectively, compared with participants with a favorable genetic score. However, addition of genetic data to clinical risk factors that included body mass index only slightly improved DM prediction. Conclusions.In white HIV-infected persons treated with antiretroviral therapy, the DM effect of genetic variants was larger than the potential toxic effects of antiretroviral therapy. SNPs contributed significantl to DM risk, but their addition to a clinical model improved DM prediction only slightly, similar to studies in the general population