The objective of this study is to investigate whether certain alleles in polymorphic genes encoding cytokines or heat shock protein in the mother and/or neonate vary among different ethnic groups and are associated with an increased risk for preterm delivery, premature membrane rupture and/or morbidity in premature neonates. Polymorphism in cytokine genes have been associated with variations in cytokine levels. Infection-related preterm birth has been shown to be initiated via induction of pro-inflammatory cytokines. High producers of a specific cytokine may have an altered susceptibility to adverse pregnancy outcome as compared to low cytokine producers. Differences in heat shock protein expression may also influence the magnitude of the host immune response. The frequency of allelic polymorphisms in genes encoding interleukin (IL)-1beta, interleukin 1 receptor antagonist (IL-lra), tumor necrosis factor (TNF)-a., IL-4 and the 70kDa heat shock protein (hsp70) will be studied in relation to preterm membrane rupture, preterm labor and delivery and neonatal morbidity. Single nucleotide polymorphisms in the IL-lbeta, TNF-a, IL-4 and hsp70 genes and a length polymorphism in intron 2 of the IL-lL-1ra gene will be evaluated. A case-control study will be performed to evaluate the relationship between ethnicity, preterm delivery and polymorphism in these genes in mother and child. Samples (buccal swabs) for genetic analysis will be collected from women with preterm premature rupture of membranes, in preterm labor who either progress to a preterm birth (<32 weeks) or who deliver at term and where the placenta and umbilical cord will be available for histopathological analysis. Control patients will be woman with an uncomplicated antepartum course, labor and delivery) who deliver a term neonate with no evidence of infection. A cohort study will also be performed to investigate the relationship between ethnicity, systemic fetal inflammatory response, fetal morbidity, and polymorphism in the above genes. The cohort will consist of the case patients and their children mentioned above stratified for the presence or absence of neonatal morbidity: necrotizing enterocolitis, periventricular leukomalacia, arrested lung development and bronchopulmonary dysplasia. Identification of genetic factors in mothers or their neonates that influence susceptibility to preterm labor and fetal morbidity in different racial groups will aid in development of improved protocols for monitoring and treatment.
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