Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth.
OBJECTIVE
To understand the differences in genetic interactions among tumor necrosis factor-alpha, interleukin-6 and their receptor gene variants between black and white patients in spontaneous preterm birth.


METHODS
Maternal and fetal DNA (n = 1195) were collected from cases (preterm birth < 36 weeks' gestation; n = 448), controls (> 37 weeks' gestation; n = 747), and genotyped for single nucleotide polymorphisms in tumor necrosis factor-alpha, tumor necrosis factor receptor 1, and tumor necrosis factor receptor 2, interleukin-6, and interleukin-6 receptor loci. Multifactor dimensionality reduction analysis was used to test all single and multilocus combinations for the ability to predict pregnancy outcome.


RESULTS
In white patients, multilocus interactions in maternal DNA between single nucleotide polymorphisms at -7227 (interleukin-6), 22,215 (interleuki-6 receptor) and -3448 (tumor necrosis factor-alpha) was predictive of approximately 59.1% (P < .02; odds ratio, 2.3 [95% confidence interval = 1.6-3.4]) of pregnancy outcome. In white fetal DNA and black maternal DNA, no significant interactive models were observed. In black patients, the best epistatic model was in fetal DNA between single nucleotide polymorphisms at 17,691 (tumor necrosis factor-receptor 1) and at -3448 (tumor necrosis factor-alpha) and was predictive of pregnancy outcome 68.3% of the time (P < .01; odds ratio, 5.0 [95% confidence interval = 2.6-9.6]).


CONCLUSIONS
Analyses of multilocus interactions found/associated different models in black and white patients in both maternal and fetal DNA with preterm birth as outcome. Significant maternal-fetal interactions were not detected in either race.
Perinatal Research Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
Stephen J
SJ
Fortunato
Ramkumar
R
Menon
Digna R
DR
Velez
Poul
P
Thorsen
Scott M
SM
Williams
D000328:Adult; D044383:Black People / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000208:ethnology / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044465:White People / Q000235:genetics*
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D004247:DNA