title: Genetic predisposition to elevated levels of C-reactive protein is associated with a decreased risk for preeclampsia.
abstract: OBJECTIVE
  To examine the association between genetic predisposition to elevated C-reactive protein (CRP)and risk for preeclampsia using validated genetic loci for C-reactive protein.
  
  
  METHODS
  Preeclampsia cases (n = 177) and normotensive controls (n = 116) were selected from live birth certificates to nulliparous Iowa women during the period August 2002-May 2005. Disease status was verified by the medical chart review. Genetic predisposition to CRP was estimated by a genetic risk score on the basis of established loci for CRP levels. Logistic regression analyses were used to evaluate the relationships between the genotype score and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry.
  
  
  RESULTS
  The genetic risk score (GRS) related to higher levels of CRP demonstrated a significantly decreased risk of preeclampsia (OR 0.89, 95% CI 0.82-0.96). When the GRS was analyzed by quartile, an inverse linear trend was observed (p = 0.0006). The results were similar after adjustments for the body mass index (BMI), smoking, and leisure-time physical activity. In the independent replication population, the association with the CRP GRS was also marginally significant (OR 0.97, 95% CI 0.92, 1.02). Meta-analysis of the two studies was statistically significant (OR 0.95, 95% CI 0.90, 0.99).
  
  
  CONCLUSIONS
  Our data suggest an inverse, counterintuitive association between the genetic predisposition to elevated levels of CRP and a decreased risk of preeclampsia. This suggests that the blood CRP level is a marker of preeclampsia, but it does not appear to be a factor on the causal pathway.
authors.affiliation: a Department of Epidemiology , University of Iowa College of Public Health , Iowa City , Iowa , USA.
authors.forename: Cassandra N
authors.initials: CN
authors.lastname: Spracklen
authors.affiliation: a Department of Epidemiology , University of Iowa College of Public Health , Iowa City , Iowa , USA.
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Smith
authors.affiliation: a Department of Epidemiology , University of Iowa College of Public Health , Iowa City , Iowa , USA.
authors.forename: Audrey F
authors.initials: AF
authors.lastname: Saftlas
authors.affiliation: b Department of Epidemiology, Division of Biology and Medicine , Brown University , Providence , Rhode Island , USA.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Triche
authors.affiliation: c Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital , Boston , Massachusetts , USA.|d Program in Medical and Population Genetics, Broad Institute , Cambridge , Massachusetts , USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bjonnes
authors.affiliation: e Department of Surgery, Penn Transplant Institute, Perelman School of Medicine , University of Pennsylvania , Philadelphia , Pennsylvania , USA.|f Division of Genetics, The Children's Hospital of Philadelphia , Philadelphia , Pennsylvania , USA.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Keating
authors.affiliation: c Center for Human Genetic Research and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital , Boston , Massachusetts , USA.|d Program in Medical and Population Genetics, Broad Institute , Cambridge , Massachusetts , USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.affiliation: g Department of Biostatistics, University of Iowa College of Public Health , Iowa City , Iowa , USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Breheny
authors.affiliation: h Division of Chronic Disease Epidemiology, Yale School of Public Health , New Haven , Connecticut , USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Dewan
authors.affiliation: a Department of Epidemiology , University of Iowa College of Public Health , Iowa City , Iowa , USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.affiliation: i Department of Environmental Health Sciences, Yale School of Public Health , New Haven , Connecticut , USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.affiliation: a Department of Epidemiology , University of Iowa College of Public Health , Iowa City , Iowa , USA.
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
mesh_terms: D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000097:blood* / Q000235:genetics; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
keywords: C-reactive protein; genetic epidemiology; genetic risk score; preeclampsia