title: Is variation in copy number of the human beta defensin gene cluster associated with preterm birth?
abstract: BACKGROUND
  Increased expression of antimicrobial peptides including human beta defensins (HBD) has been reported in the amniotic fluid and vaginal secretions of women who deliver preterm. We have previously shown that these women have increased first trimester serum HBD2. The gene encoding HBD2, DEFB4A, is part of a defensin beta (DEFB) cluster on chromosome 8 that is variable in copy number. Increased serum HBD2 is associated with increased DEFB copy number. We aimed to test the hypothesis that variation in DEFB copy number is associated with preterm birth.
  
  
  METHODS
  In a retrospective, case-control study, genomic DNA and serum were extracted from blood collected from white European women at 11-13 weeks' gestation attending King's College Hospital between March 1, 2006, and Sept 30, 2010. DEFB copy number was determined by paralogue ratio test. Serum HBD2 concentration was measured by ELISA. Data were analysed with Pearson correlation (Excel, version 2010) and binary logistic regression (SPSS, version 20).
  
  
  RESULTS
  Cases were 102 women who either delivered preterm in the index pregnancy or had a history of preterm delivery. Controls were 152 women who had had at least one previous term delivery and delivered at term in the index pregnancy; they had no history of preterm birth. Modal copy number was 4 (range 2-7). Serum was available from 140 women (30 cases, 54 controls, 56 not included in the genetic association study). Median HBD2 concentration was 761·5 pg/mL (IQR 449·6-1232·0). There was no association between DEFB copy number and preterm birth, nor was there a correlation between copy number and serum HBD2 concentration.
  
  
  CONCLUSIONS
  Although variation in HBD2 protein expression in the first trimester might be useful to predict risk of preterm birth, we found no association between DEFB copy number and preterm birth. Nor did we find a correlation between DEFB copy number and serum HBD2 expression in the first trimester of pregnancy; this might be due to variation in regulatory sequences-some of which are progesterone and oestrogen sensitive-between individual copies.
  
  
  BACKGROUND
  Wellcome Trust, Wellbeing of Women.
authors: Research Department of Maternal and Fetal Medicine, Institute for Women's Health, University College London, London, UK; Infection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health, University College London, London, UK. Electronic address: catherine.james@ucl.ac.uk.
authors: Catherine
authors: C
authors: James
authors: Department of Genetics, University of Leicester, Leicester, UK.
authors: Razan
authors: R
authors: Abujaber
authors: Infection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health, University College London, London, UK.
authors: Mona
authors: M
authors: Bajaj-Elliott
authors: Harris Birthright Research Centre of Fetal Medicine, King's College Hospital, London, UK.
authors: Argyro
authors: A
authors: Syngelaki
authors: Infection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health, University College London, London, UK.
authors: Nigel
authors: N
authors: Klein
authors: Harris Birthright Research Centre of Fetal Medicine, King's College Hospital, London, UK.
authors: Kypros
authors: K
authors: Nicolaides
authors: Department of Genetics, University of Leicester, Leicester, UK.
authors: Edward
authors: E
authors: Hollox
authors: Research Department of Maternal and Fetal Medicine, Institute for Women's Health, University College London, London, UK.
authors: Donald
authors: D
authors: Peebles