title: Adiponectin gene polymorphisms and acute respiratory distress syndrome susceptibility and mortality.
abstract: BACKGROUND
  Adiponectin is an anti-inflammatory adipokine that is the most abundant gene product of adipose tissue. Lower levels have been observed in obesity, insulin resistance, and in critical illness. However, elevated levels early in acute respiratory failure have been associated with mortality. Polymorphisms in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined for relationships with obesity, insulin resistance and diabetes, cardiovascular disease, and to circulating adipokine levels, but many gaps in knowledge remain. The current study aims to assess the association between potentially functional polymorphisms in adiponectin-related genes with acute respiratory distress syndrome (ARDS) risk and mortality.
  
  
  METHODS
  Consecutive patients with risk factors for ARDS admitted to the ICU were enrolled and followed prospectively for development of ARDS. ARDS cases were followed through day 60 for all-cause mortality. 2067 patients were successfully genotyped using the Illumina CVD BeadChip high-density platform. Of these, 567 patients developed ARDS. Forty-four single nucleotide polymorphisms (SNPs) on ADIPOQ, ADIPOR1 and ADIPOR2 were successfully genotyped. Of these, 9 SNPs were hypothesized to be functional based on their location (promoter, exon, or 3' untranslated region). These 9 SNPs were analyzed for association with ARDS case status and mortality among ARDS cases.
  
  
  RESULTS
  After multivariable analysis and adjustment for multiple comparisons, no SNPs were significantly associated with ARDS case status. Among ARDS cases, homozygotes for the minor allele of rs2082940 (ADIPOQ) had increased mortality (hazard ratio 2.61, 95% confidence interval 1.36-5.00, p = 0.0039) after adjustment for significant covariates. The significance of this association persisted after adjustment for multiple comparisons (FDR_q = 0.029).
  
  
  CONCLUSIONS
  A common and potentially functional polymorphism in ADIPOQ may impact survival in ARDS. Further studies are required to replicate these results and to correlate genotype with circulating adiponectin levels.
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Ahasic
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chau-Chyun
authors.initials: CC
authors.lastname: Sheu
authors.affiliation: Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.affiliation: Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America ; Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000208:Acute Disease; D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000401:mortality*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin