title: Preeclampsia and cardiovascular disease share genetic risk factors on chromosome 2q22.
abstract: OBJECTIVE
  Four putative single nucleotide polymorphism (SNP) risk variants at the preeclampsia susceptibility locus on chromosome 2q22; rs2322659 (LCT), rs35821928 (LRP1B), rs115015150 (RND3) and rs17783344 (GCA), were recently shown to associate with known cardiovascular risk factors in a Mexican American cohort. This study aimed to further evaluate the pleiotropic effects of these preeclampsia risk variants in an independent Australian population-based cohort.
  
  
  METHODS
  The four SNPs were genotyped in the Western Australian Pregnancy Cohort (Raine) Study that included DNA, clinical and biochemical data from 1246 mothers and 1404 of their now adolescent offspring. Genotype association analyses were undertaken using the SOLAR software.
  
  
  RESULTS
  Nominal associations (P<0.05) with cardiovascular risk factors were detected for all four SNPs. The LCT SNP was associated with decreased maternal height (P=0.005) and decreased blood glucose levels in adolescents (P=0.022). The LRP1B SNP was associated with increased maternal height (P=0.026) and decreased maternal weight (P=0.044). The RND3 SNP was associated with decreased triglycerides in adolescents (P=0.001). The GCA SNP was associated with lower risk in adolescents to be born of a preeclamptic pregnancy (P=0.003) and having a mother with prior preeclamptic pregnancy (P=0.033).
  
  
  CONCLUSIONS
  Our collective findings support the hypothesis that genetic mechanisms for preeclampsia and CVD are, at least in part, shared, but need to be interpreted with some caution as a Bonferroni correction for multiple testing adjusted the statistical significance threshold (adjusted P<0.001).
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway. Electronic address: mari.loset@gmail.com.
authors.forename: Mari
authors.initials: M
authors.lastname: Løset
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.affiliation: Centre for Genetic Origins of Health and Disease, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Phillip E
authors.initials: PE
authors.lastname: Melton
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Ang
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6000, Australia; Telethon Institute for Child Health Research, The University of Western Australia, Perth, WA 6008, Australia.
authors.forename: Rae-Chi
authors.initials: RC
authors.lastname: Huang
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6000, Australia.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Perth, WA 6000, Australia.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Beilin
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: Pennell
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway; Central Norway Regional Health Authority (RHA), N-7501 Stjørdal, Norway.
authors.forename: Linda T
authors.initials: LT
authors.lastname: Roten
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway; Centre of Molecular Inflammation Research, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Iversen
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway; Centre of Molecular Inflammation Research, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway.
authors.forename: Rigmor
authors.initials: R
authors.lastname: Austgulen
authors.affiliation: Department of Perinatal Medicine, Royal Women's Hospital, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Obstetrics & Gynaecology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Christine E
authors.initials: CE
authors.lastname: East
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Perinatal Medicine, Royal Women's Hospital, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Obstetrics & Gynaecology, The University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Brennecke
authors.affiliation: Centre for Genetic Origins of Health and Disease, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
keywords: 2q22; Cardiovascular disease (CVD); Genetic association; Preeclampsia; Raine Study