Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants

• Type of Material: Article
• Authors: Ramkumar Menon, Emory University; Brad Pearce, Emory University; Digna R Velez, Emory University; Mario Merialdi, World Health Organization; Scott M Williams, Vanderbilt University; Stephen J Fortunato, Emory University; Poul Thorsen, Emory University
• Language: English
• Date: 2009-06-15
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2009 Menon et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1186%2F1477-7827-7-62
• Title of Journal or Parent Work: Reproductive Biology and Endocrinology
• Volume: 7
• Start Page: 62
• End Page: 62
• Grant/Funding Information: We gratefully acknowledge research support from the Perinatal Research Initiative funds from March of Dimes, USA (RM), Elsass foundation, Denmark (RM), Thrasher Research Funds (SJF), the National Institutes of Health, NIMH grant 5R21MH68513 (to BDP) and the NARSAD Young Investigator Award (BDP).
• Research Categories: Health Sciences, Pathology; Health Sciences, Epidemiology; Biology, Genetics

Abstract

Objective: To study pathophysiologic pathways in spontaneous preterm birth and possibly the racial disparity associating with maternal and fetal genetic variations, using bioinformatics tools. Methods: A large scale candidate gene association study was performed on 1442 SNPs in 130 genes in a case (preterm birth < 36 weeks) control study (term birth > 37 weeks). Both maternal and fetal DNA from Caucasians (172 cases and 198 controls) and 279 African-Americans (82 cases and 197 controls) were used. A single locus association (genotypic) analysis followed by hierarchical clustering was performed, where clustering was based on p values for significant associations within each race. Using Ingenuity Pathway Analysis (IPA) software, known pathophysiologic pathways in both races were determined. Results: From all SNPs entered into the analysis, the IPA mapped genes to specific disease functions. Gene variants in Caucasians were implicated in disease functions shared with other known disorders; specifically, dermatopathy, inflammation, and hematological disorders. This may reflect abnormal cervical ripening and decidual hemorrhage. In African-Americans inflammatory pathways were the most prevalent. In Caucasians, maternal gene variants showed the most prominent role in disease functions, whereas in African Americans it was fetal variants. The IPA software was used to generate molecular interaction maps that differed between races and also between maternal and fetal genetic variants. Conclusion: Differences at the genetic level revealed distinct disease functions and operational pathways in African Americans and Caucasians in spontaneous preterm birth. Differences in maternal and fetal contributions in pregnancy outcome are also different between African Americans and Caucasians. These results present a set of explicit testable hypotheses regarding genetic associations with preterm birth in African Americans and Caucasians