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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-40552

Rotger, M; Gsponer, T; Martinez, R; Taffé, P; Elzi, L; Vernazza, P; Cavassini, M; Bernasconi, E; Hirschel, B; Furrer, H; Weber, R; Ledergerber, B; Egger, M; Telenti, A; Tarr, P E; Swiss HIV Cohort Study, (2010). Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals. Clinical Infectious Diseases, 51(9):1090-1098.

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Abstract

BACKGROUND: Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficiency 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 identified 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% confidence 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 significantly to DM risk, but their addition to a clinical model improved DM prediction only slightly, similar to studies in the general population.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
DDC:610 Medicine & health
Language:English
Date:2010
Deposited On:16 Jan 2011 17:11
Last Modified:16 Jan 2014 01:14
Publisher:University of Chicago Press
ISSN:1058-4838
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1086/656630
PubMed ID:20879858
Citations:Web of Science®. Times Cited: 6
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Scopus®. Citation Count: 8

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