Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants
ABSTRACT The objective of the study was to study the genetic risk factors of spontaneous preterm birth (PTB) in African Americans.
Case-control analyses were performed using maternal and fetal deoxyribonucleic acid from 279 African American birth events (82 PTB and 197 term) and 1432 single-nucleotide polymorphisms from 130 candidate genes. Single-locus association and haplotype analyses were performed.
The most significant associations were in the maternal interleukin (IL)-15 (rs10833, allele P = 2.91 x 10(-4), genotype P = 2.00 x 10(-3)) gene and the fetal IL-2 receptor B (IL-2RB) (rs84460, allele P = 1.37 x 10(-4), genotype P = 6.29 x 10(-4)) gene. The best models for these markers were additive (rs10833, odds ratio [OR], 0.30; 95% confidence interval [CI], 0.14-0.62; P = 1.0 x 10(-3); rs84460, OR, 2.32; 95% CI, 1.47-3.67; P < 1.0 x 10(-3)). The largest number of significant associations was found in genes related to infection and inflammation. There were overall a larger number of significant associations in infants than in mothers.
These results support a strong role for genes involved in infection and inflammation in the pathogenesis of PTB, particularly IL-12 and IL-12RB, and indicate that in African Americans there may be complementarity of maternal and fetal genetic risks for PTB.
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ABSTRACT: OBJECTIVE: During pregnancy, 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) is involved in the development of the placental barrier, and its main function is to protect the fetus from the effects of the physiological increase of maternal glucocorticoids. We compared human placental gene expression patterns of 11β-HSD2 from pregnancies that ended with preterm delivery versus full term pregnancies as controls. STUDY DESIGN: We used real-time PCR to assess the placental gene expression patterns of 11β-HSD2 in 104 preterm and 140 full term pregnancies (control group) at the time of delivery. RESULTS: In the preterm delivery group, the proportion of smokers was 26.9%, significantly higher than in the control group. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. The 11β-HSD2 gene was underexpressed in the preterm delivery group compared to normal pregnancy between 28 and 36 gestational weeks, but unchanged between 24 and 28 weeks. There was no fetal gender effect on 11β-HSD2 gene expression. CONCLUSION: The reduced activity of the 11β-HSD2 gene seen in the preterm delivery group may impair fetal defences against maternal glucocorticoid exposure. In cases of impending premature delivery, glucocorticoid effects, potentially including postnatal neurological abnormalities and growth restriction, may be worsened by prophylactic steroids given to accelerate fetal lung maturity. The impairment in fetal defences against maternal glucocorticoids due to reduced 11β-HSD2 enzyme activity appears to begin after gestational week 28.European journal of obstetrics, gynecology, and reproductive biology 09/2012; 165(2). DOI:10.1016/j.ejogrb.2012.08.009 · 1.63 Impact Factor
- The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 01/2009; 22 Suppl 2:5-23. DOI:10.1080/14767050902860690 · 1.21 Impact Factor
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ABSTRACT: Very preterm birth (<32 weeks' gestation) occurs in approximately 2% of livebirths but is a leading cause of infant mortality and morbidity in the United States. African-American women have a 2-fold to 3-fold elevated risk compared with non-Hispanic white women for reasons that are incompletely understood. This paper reviews the evidence for the biologic and social patterning of very preterm birth, with attention to leading hypotheses regarding the etiology of the racial disparity. A systematic review of the literature in the MEDLINE, CINAHL, PsycInfo, and EMBASE indices was conducted. The literature to date suggests a complex, multifactorial causal framework for understanding racial disparities in very preterm birth, with maternal inflammatory, vascular, or neuroendocrine dysfunction as proximal pathways and maternal exposure to stress, racial differences in preconceptional health, and genetic, epigenetic, and gene-environment interactions as more distal mediators. Interpersonal and institutionalized racism are mechanisms that may drive racially patterned differences. Current literature is limited in that research on social determinants and biologic processes of prematurity has been generally disconnected. Improved etiologic understanding and the potential for effective intervention may come with better integration of these research approaches.Epidemiologic Reviews 06/2009; 31:84-98. DOI:10.1093/ajerev/mxp003 · 7.33 Impact Factor