title: Two novel genetic variants in the mineralocorticoid receptor gene associated with spontaneous preterm birth.
abstract: BACKGROUND
  Preterm birth is the leading cause of mortality and morbidity in newborn infants. Its etiology is multifactorial with genes and environmental factors, including chronic maternal stress, contributing to its risk. Our objective was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in the stress response are associated with spontaneous preterm birth using a candidate gene approach.
  
  
  METHODS
  A total of 210 cases (singleton spontaneous preterm birth at <37 weeks) and 412 controls (singleton term birth at 38-42 weeks without a history of preterm birth) were studied. High quality maternal DNA was available from saliva samples of 190 cases and 369 controls and compared. Sociodemographic and medical data were collected. Sixteen SNPs, either tag SNPs located in key genes involved in the stress response identified in the Preterm Birth Genome Project database or SNPs found to be associated with adverse mental health outcomes in the published literature, were selected for genotyping and sequencing. SNPs were genotyped using Taqman SNP genotyping assays. Univariate and multivariate logistic regression were performed.
  
  
  RESULTS
  Multivariate analysis showed that two SNPs located in the mineralocorticoid receptor gene were significantly associated with spontaneous preterm birth: rs17484063 (OR 0.50, p = 0.038) and rs2883929 (OR 0.49, p = 0.017), regardless of maternal age, smoking, alcohol use, educational status, and history of spontaneous miscarriage.
  
  
  CONCLUSIONS
  This report demonstrates an association between mineralocorticoid receptor gene polymorphisms, rs17484063 and rs2883929, and preterm birth, supporting a role for genetics in the association between chronic maternal stress and preterm birth. Potentially, this information may be used to predicting the risk of having a preterm delivery.
authors.affiliation: Obstetrics and Gynaecology, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. ingechristiaens@doctors.org.uk.
authors.forename: Inge
authors.initials: I
authors.lastname: Christiaens
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, 6009, WA, Australia. aqw07398@hotmail.com.
authors.forename: Q Wei
authors.initials: QW
authors.lastname: Ang
authors.affiliation: Department of Genetics, Dartmouth College, Hanover, NH 03755, USA. Lindsay.N.Gordon.GR@dartmouth.edu.
authors.forename: Lindsay N
authors.initials: LN
authors.lastname: Gordon
authors.affiliation: Departments of Obstetrics and Gynecology and Pediatrics, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada. xin.fang@ualberta.ca.
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Genetics, Dartmouth College, Hanover, NH 03755, USA. Scott.Williams@dartmouth.edu.|Center for Human Genetics Research, Vanderbilt University, Nashville, TN, 37232-0700, USA. Scott.Williams@dartmouth.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, 6009, WA, Australia. craig.pennell@uwa.edu.au.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.affiliation: Departments of Obstetrics and Gynecology and Pediatrics, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada. david.olson@ualberta.ca.
authors.forename: David M
authors.initials: DM
authors.lastname: Olson
mesh_terms: D014644:Genetic Variation; D060005:Genotyping Techniques; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D047928:Premature Birth / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*
chemical_list: D018161:Receptors, Mineralocorticoid