Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.

Details

Serval ID
serval:BIB_432AEAE1B086
Type
Article: article from journal or magazin.
Collection
Publications
Title
Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.
Journal
Clinical Infectious Diseases
Author(s)
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.
Working group(s)
Swiss HIV Cohort Study
Contributor(s)
Battegay M., Bernasconi E., Böni J., Bucher HC., Bürgisser P., Calmy A., Cattacin S., Cavassini M., Dubs R., Egger M., Elzi L., Fischer M., Flepp M., Fontana A., Francioli P., Furrer H., Fux C., Gorgievski M., Günthard H., Hirsch H., Hirschel B., Hösli I., Kahlert Ch., Kaiser L., Karrer U., Kind C., Klimkait T., Ledergerber B., Martinetti G., Martinez B., Müller N., Nadal D., Opravil M., Paccaud F., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schüpbach J., Speck R., Taffé P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1537-6591 (Electronic)
ISSN-L
1058-4838
Publication state
Published
Issued date
2010
Volume
51
Number
9
Pages
1090-1098
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Anti-HIV Agents/therapeutic use, Diabetes Mellitus/epidemiology, Diabetes Mellitus/genetics, European Continental Ancestry Group, Genetic Predisposition to Disease, HIV Infections/complications, HIV Infections/drug therapy, Humans, Incidence, Polymorphism, Single Nucleotide, Risk Factors, Switzerland
Pubmed
Web of science
Open Access
Yes
Create date
11/11/2010 10:58
Last modification date
08/05/2019 17:46
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