title: Associations between gene polymorphisms in fatty acid metabolism pathway and preterm delivery in a US urban black population.
abstract: There is increasing evidence suggesting that higher intakes of fish or n-3 polyunsaturated fatty acids supplements may decrease the risk of preterm delivery (PTD). We hypothesized that genetic variants of the enzymes critical to fatty acids biosynthesis and metabolism may be associated with PTD. We genotyped 231 potentially functional single nucleotide polymorphisms (SNPs) and tagSNPs in 9 genes (FADS1, FADS2, PTGS1, PTGS2, ALOX5, ALOX5AP, PTGES, PTGES2, and PTGES3) among 1,110 black mothers, including 542 mothers who delivered preterm (<37 weeks gestation) and 568 mothers who delivered full-term babies (≥37 weeks gestation) at Boston Medical Center. After excluding SNPs that are in complete linkage disequilibrium or have lower minor allele frequency (<1%) or call rate (<90%), we examined the association of 206 SNPs with PTD using multiple logistic regression models. We also imputed 190 HapMap SNPs via program MACH and examined their associations with PTD. Finally, we explored gene-level and pathway-level associations with PTD using the adaptive rank truncated product (ARTP) methods. A total of 21 SNPs were associated with PTD (p value ranging from 0.003 to 0.05), including 3 imputed SNPs. Gene-level ARTP statistics indicated that the gene PTGES2 was significantly associated with PTD with a gene-based p value equal to 0.01. No pathway-based association was found. In this large and comprehensive candidate gene study, we found a modest association of genes in fatty acid metabolism pathway with PTD. Further investigation of these gene polymorphisms jointly with fatty acid measures and other genetic factors would help better understand the pathogenesis of PTD.
authors.affiliation: Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital, Children's Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. xnliu@childrensmemorial.org
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Guoying
authors.initials: G
authors.lastname: Wang
authors.forename: Xiumei
authors.initials: X
authors.lastname: Hong
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Shanchun
authors.initials: S
authors.lastname: Zhang
authors.forename: Hongjian
authors.initials: H
authors.lastname: Wang
authors.forename: Colleen
authors.initials: C
authors.lastname: Pearson
authors.forename: Katherin
authors.initials: K
authors.lastname: Ortiz
authors.forename: Deli
authors.initials: D
authors.lastname: Wang
authors.forename: Emmet
authors.initials: E
authors.lastname: Hirsch
authors.forename: Barry
authors.initials: B
authors.lastname: Zuckerman
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics*; D000090943:Delta-5 Fatty Acid Desaturase; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D014505:Urban Population; D055815:Young Adult
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005227:Fatty Acids; C000716847:FADS1 protein, human