Genetic polymorphisms of hemostasis genes and primary outcome of very low birth weight infants.
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.
Härtel
Christoph
C
Department of Pediatrics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
König
Inke
I
Köster
Stefan
S
Kattner
Evelyn
E
Kuhls
Eckhardt
E
Küster
Helmut
H
Möller
Jens
J
Müller
Dirk
D
Kribs
Angela
A
Segerer
Hugo
H
Wieg
Christian
C
Herting
Egbert
E
Göpel
Wolfgang
W
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*
D020413:3' Untranslated Regions; C095381:factor V Leiden; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D005176:Factor XIII