title: Genetic polymorphisms of hemostasis genes and primary outcome of very low birth weight infants.
abstract: BACKGROUND
  Recent investigations have reported an influence of thrombophilic mutations and antithrombotic risk factors with development of intraventricular hemorrhage. It was our objective for this study to investigate the impact of genetic polymorphisms of hemostasis genes on the primary outcome measures of sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and periventricular leukomalacia in a large cohort of very low birth weight infants.
  
  
  METHODS
  There were 586 very low birth weight infants enrolled prospectively in a multicenter trial between September 2003 and July 2005, and an additional 595 very low birth weight infants, who had been recruited in a previous prospective trial, were studied. DNA samples were taken by buccal swab, and genotypes of factor V Leiden mutation, prothrombin G20210A mutation, the factor VII-323 del/ins polymorphism, and the factor XIII-Val34Leu polymorphisms were determined by polymerase chain reaction and restriction enzyme digestion.
  
  
  RESULTS
  In contrast to data published previously, the frequency of intraventricular hemorrhage or periventricular leukomalacia was not significantly influenced by any of the genetic variants tested. Carriers of the factor XIII-Val34Leu polymorphism, however, had a higher sepsis rate and a longer period of hospital care compared with noncarriers. The factor VII-323 del/ins polymorphism was found to be a potential protective factor against bronchopulmonary dysplasia.
  
  
  CONCLUSIONS
  We could not confirm previously reported associations of hemostasis gene variants and development of intraventricular hemorrhage in very low birth weight infants. To better understand gene-disease associations in very low birth weight infants, the prospective development of large-scale cohorts with well-defined phenotypes and corresponding DNA samples is essential.
authors.affiliation: Department of Pediatrics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
authors.forename: Inke
authors.initials: I
authors.lastname: König
authors.forename: Stefan
authors.initials: S
authors.lastname: Köster
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kattner
authors.forename: Eckhardt
authors.initials: E
authors.lastname: Kuhls
authors.forename: Helmut
authors.initials: H
authors.lastname: Küster
authors.forename: Jens
authors.initials: J
authors.lastname: Möller
authors.forename: Dirk
authors.initials: D
authors.lastname: Müller
authors.forename: Angela
authors.initials: A
authors.lastname: Kribs
authors.forename: Hugo
authors.initials: H
authors.lastname: Segerer
authors.forename: Christian
authors.initials: C
authors.lastname: Wieg
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020016:Activated Protein C Resistance / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D002404:Catheterization / Q000706:statistics & numerical data; D002543:Cerebral Hemorrhage / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics; D005167:Factor VII / Q000235:genetics; D005168:Factor VII Deficiency / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D005176:Factor XIII / Q000235:genetics; D005177:Factor XIII Deficiency / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006474:Hemorrhagic Disorders / Q000150:complications / Q000235:genetics*; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D019102:Infant, Very Low Birth Weight; D007969:Leukomalacia, Periventricular / Q000453:epidemiology / Q000209:etiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D018805:Sepsis / Q000453:epidemiology / Q000209:etiology; D017384:Sequence Deletion; D013514:Surgical Procedures, Operative / Q000706:statistics & numerical data; D019851:Thrombophilia / Q000150:complications / Q000151:congenital / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C095381:factor V Leiden; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D005176:Factor XIII