title: Maternal single nucleotide polymorphisms in the fatty acid desaturase 1 and 2 coding regions modify the impact of prenatal supplementation with DHA on birth weight.
abstract: BACKGROUND
  Specific single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene affect the activity and efficiency of enzymes that are responsible for the conversion of polyunsaturated fatty acids (PUFAs) into their long-chain active form. A high prevalence of SNPs that are associated with slow PUFA conversion has been described in Hispanic populations.
  
  
  OBJECTIVE
  We assessed the heterogeneity of the effect of prenatal supplementation with docosahexaenoic acid (DHA) on birth weight across selected FADS SNPs in a sample of Mexican women and their offspring.
  
  
  METHODS
  We obtained information on the maternal genotype from stored blood samples of 654 women who received supplementation with 400 mg DHA/d or a placebo from weeks 18 to 22 of gestation through delivery as part of a randomized controlled trial conducted in Cuernavaca, Mexico. We selected 4 tag SNPs (rs174455, rs174556, rs174602, and rs498793) in the FADS region for analysis. We used an ANOVA to test for the heterogeneity of the effect on birth weight across each of the 4 SNPs.
  
  
  RESULTS
  The mean ± SD birth weight was 3210 ± 470 g, and the weight-for-age z score (WAZ) was -0.24 ± 1.00. There were no intention-to-treat differences in birth weights. We showed significant heterogeneity by SNP rs174602 (P= 0.02); offspring of carriers of alleles TT and TC in the intervention group were heavier than those in the placebo group (WAZ: -0.13 ± 0.14 and -0.20 ± 0.08 compared with -0.55 ± 0.15 and -0.39 ± 0.09, respectively); there were no significant differences in offspring of rs174602 CC homozygotes (WAZ: -0.26 ± 0.09 in the intervention group compared with -0.04 ± 0.09 in the placebo group). We showed no significant heterogeneity across the other 3 FADS SNPs.
  
  
  CONCLUSIONS
  Differential responses to prenatal DHA supplementation on the basis of the genetic makeup of target populations could explain the mixed evidence of the impact of DHA supplementation on birth weight. This trial was registered at clinicaltrials.gov as NCT00646360.
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA;
authors.forename: Ines
authors.initials: I
authors.lastname: Gonzalez-Casanova
authors.affiliation: Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Centre, Munich, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Rzehak
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA;
authors.forename: Aryeh D
authors.initials: AD
authors.lastname: Stein
authors.affiliation: Health and Nutrition Research Center and.
authors.forename: Raquel
authors.initials: R
authors.lastname: Garcia Feregrino
authors.affiliation: Health and Nutrition Research Center and.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rivera Dommarco
authors.affiliation: Population Health Research Center, National Institute of Public Health, Cuernavaca, Mexico; and.
authors.forename: Albino
authors.initials: A
authors.lastname: Barraza-Villarreal
authors.affiliation: Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Centre, Munich, Germany;
authors.forename: Hans
authors.initials: H
authors.lastname: Demmelmair
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.affiliation: Health and Nutrition Research Center and.
authors.forename: Salvador
authors.initials: S
authors.lastname: Villalpando
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA;
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Martorell
authors.affiliation: Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Centre, Munich, Germany;
authors.forename: Berthold
authors.initials: B
authors.lastname: Koletzko
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA; uramakr@emory.edu.
authors.forename: Usha
authors.initials: U
authors.lastname: Ramakrishnan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016718:Arachidonic Acid / Q000097:blood; D001724:Birth Weight / Q000187:drug effects*; D000090943:Delta-5 Fatty Acid Desaturase; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000097:blood; D004311:Double-Blind Method; D002149:Energy Intake; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D016014:Linear Models; D008297:Male; D008800:Mexico; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011295:Prenatal Care; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human
keywords: DHA; FADS; birth weight; long-chain PUFAs; prenatal supplementation