title: Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.
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.
authors.affiliation: Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: Margalida
authors.initials: M
authors.lastname: Rotger
authors.forename: Thomas
authors.initials: T
authors.lastname: Gsponer
authors.forename: Raquel
authors.initials: R
authors.lastname: Martinez
authors.forename: Patrick
authors.initials: P
authors.lastname: Taffé
authors.forename: Luigia
authors.initials: L
authors.lastname: Elzi
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Philip E
authors.initials: PE
authors.lastname: Tarr
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013557:Switzerland; D044465:White People
chemical_list: D019380:Anti-HIV Agents