Preterm birth in African Americans is associated with infection and inflammatory response gene variants

Dr John T. Macdonald Foundation Department of Human Genetics and Miami Institute of Human Genomics, University of Miami, Miami, FL, USA.
American journal of obstetrics and gynecology (Impact Factor: 4.7). 11/2008; 200(2):209.e1-27. DOI: 10.1016/j.ajog.2008.08.051
Source: PubMed


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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    • "Several epidemiological studies revealed the importance of genetic factors in the background of preterm deliveries [4] [5]. Among these, some studies point to the role of genes involved in cholesterol metabolism [5], infection and inflammation [6] [7]. "
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    • "For example, there are racial disparities in the inflammatory response associated with PTL such as over production of IL-6 and IL-8 in Caucasian women versus an increase in IL-1β and TNF-α in African American women [37], [38]. These differences have been found to correlate with variations in single nucleotide polymorphisms (SNP) that are associated with each race [39], [40]. Polymorphism in the promoter region of TNF-α gene has been documented to be risk factor for PTL in the presence of bacterial vaginosis [41]. "
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    • "Genetic research exploring determinants of preterm birth in African American women has identified several polymorphisms associated with increased risk, including variants in a currently undefined susceptibility locus on chromosome 7 [60], tumor necrosis factor alpha (TNF-α) and tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2) [61], cytokines and cytokine-related genes [61], and in genes involved in infection and inflammation, including interleukin (IL)-12 and IL-12RB[62]. Though these observed genetic associations have been modest and for the most part unreplicated [55], they suggest that genetic variation contributing to variation in inflammation, maternal/fetal stress, uterine distension, decidual hemorrhage, and/or enzymatic metabolism may contribute to risk of preterm birth [59]. "
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