title: Genetic regulation of amniotic fluid TNF-alpha and soluble TNF receptor concentrations affected by race and preterm birth.
abstract: Racial disparity in spontaneous preterm birth (PTB) between African Americans and Caucasians in the US is unexplained, but is probably related to differences in amniotic fluid (AF) inflammatory cytokine profiles. Therefore, this study analyzed the association of 34 single nucleotide polymorphisms (SNPs) in TNF-alpha and its receptor genes (TNFR1 and TNFR2) with AF TNF-alpha and soluble TNF receptor (R1 and R2) concentrations in PTB. Samples consisted of African American and Caucasian cases (PTB), and controls (term birth) for which both cytokine, and maternal and fetal genotype data were available. Analyses were performed with genotype, case, and maker-status interaction in the model for log transformed cytokine concentrations. In Caucasians, two interactions between genotype and pregnancy outcome associated with cytokine concentrations, whereas 14 gene variants in African Americans showed interactions with pregnancy outcome, and 13 showed association with genetic markers. In conclusion, cytokine concentrations in African American preterm births can be partially explained by interactions between pregnancy outcome, SNPs and infection. This does not appear to be the case in Caucasians. These findings may be important in understanding disparity in rates of PTB between the two populations.
authors.affiliation: The Perinatal Research Center, 2300 Patterson Street, Nashville, TN 37203, USA. fortunat@edge.net
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
authors.forename: Digna R
authors.initials: DR
authors.lastname: Velez
authors.forename: Nicole
authors.initials: N
authors.lastname: Morgan
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Lombardi
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fortunato
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D044383:Black People; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics*; D044465:White People; D001741:Black or African American
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha