Role of African ancestry and gene-environment interactions in predicting preterm birth.
OBJECTIVE
To estimate whether African ancestry, specific gene polymorphisms, and gene-environment interactions could account for some of the unexplained preterm birth variance within African American women.


METHODS
We genotyped 1,509 African ancestry-informative markers, cytochrome P450 1A1 (CYP1A1), and glutathione S-transferases Theta 1 (GSTT1) variants in 1,030 self-reported African American mothers. We estimated the African ancestral proportion using the ancestry-informative markers for all 1,030 self-reported African American mothers. We examined the effect of African ancestry and CYP1A1- and GSTT1-smoking interactions on preterm birth cases as a whole and within its subgroups: very preterm birth (gestational age less than 34 weeks); and late preterm birth (gestational age greater than 34 and less than 37 weeks). We applied logistic regression and receiver operating characteristic curve analysis, separately, to evaluate whether African ancestry and CYP1A1- and GSTT1-smoking interactions could make additional contributions to preterm birth beyond epidemiologic factors.


RESULTS
We found significant associations of African ancestry with preterm birth (22% compared with 31%, odds ratio [OR] 1.11, 95% confidence interval [CI] 1.02-1.20) and very preterm birth (23% compared with 33%, OR 1.17, 95% CI 1.03-1.33), but not with late preterm birth (22% compared with 29%, OR 1.06, 95% CI 0.97-1.16). In addition, the receiver operating characteristic curve analysis suggested that African ancestry and CYP1A1- and GSTT1-smoking interactions made substantial contributions to very preterm birth beyond epidemiologic factors.


CONCLUSIONS
Our data underscore the importance of simultaneously considering epidemiologic factors, African ancestry, specific gene polymorphisms, and gene-environment interactions to better understand preterm birth racial disparity and to improve our ability to predict preterm birth, especially very preterm birth.
From the Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, Illinois; the Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; the Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Taiwan; the Department of Biostatistics and Epidemiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; the Departments of Pediatrics and Obstetrics and Gynecology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts; the Department of Obstetrics and Gynecology, North Shore University Health System, Evanston, Illinois; the Department of Obstetrics and Gynecology, Pritzker School of Medicine, University of Chicago, Chicago, Illinois; and the Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Hui-Ju
HJ
Tsai
Xiumei
X
Hong
Jinbo
J
Chen
Xin
X
Liu
Colleen
C
Pearson
Katherin
K
Ortiz
Emmet
E
Hirsch
Linda
L
Heffner
Daniel E
DE
Weeks
Barry
B
Zuckerman
Xiaobin
X
Wang
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001900:Boston / Q000453:epidemiology; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic; D011247:Pregnancy; D047928:Premature Birth / Q000208:ethnology* / Q000235:genetics; D055815:Young Adult
D019363:Cytochrome P-450 CYP1A1; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase