Journal Article

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

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

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 9, pages 1090-1098
Published in print November 2010 | ISSN: 1058-4838
Published online November 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/656630
Impact of Single Nucleotide Polymorphisms and of Clinical Risk Factors on New-Onset Diabetes Mellitus in HIV-Infected Individuals

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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.

Journal Article.  4419 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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