Integrating genetics with newborn metabolomics in infantile hypertrophic pyloric stenosis
Open Access
- 8 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Metabolomics
- Vol. 17 (1), 1-10
- https://doi.org/10.1007/s11306-020-01763-2
Abstract
Introduction Infantile hypertrophic pyloric stenosis (IHPS) is caused by hypertrophy of the pyloric sphincter muscle. Objectives Since previous reports have implicated lipid metabolism, we aimed to (1) investigate associations between IHPS and a wide array of lipid-related metabolites in newborns, and (2) address whether detected differences in metabolite levels were likely to be driven by genetic differences between IHPS cases and controls or by differences in early life feeding patterns. Methods We used population-based random selection of IHPS cases and controls born in Denmark between 1997 and 2014. We randomly took dried blood spots of newborns from 267 pairs of IHPS cases and controls matched by sex and day of birth. We used a mixed-effects linear regression model to evaluate associations between 148 metabolites and IHPS in a matched case–control design. Results The phosphatidylcholine PC(38:4) showed significantly lower levels in IHPS cases (P = 4.68 × 10−8) as did six other correlated metabolites (four phosphatidylcholines, acylcarnitine AC(2:0), and histidine). Associations were driven by 98 case–control pairs born before 2009, when median age at sampling was 6 days. No association was seen in 169 pairs born in 2009 or later, when median age at sampling was 2 days. More IHPS cases than controls had a diagnosis for neonatal difficulty in feeding at breast (P = 6.15 × 10−3). Genetic variants known to be associated with PC(38:4) levels did not associate with IHPS. Conclusions We detected lower levels of certain metabolites in IHPS, possibly reflecting different feeding patterns in the first days of life.Funding Information
- Oak Foundation
- Novo Nordisk Fonden (2010-11-12, 2009-07-28)
- Sundhed og Sygdom, Det Frie Forskningsråd (DFF 4004-00512)
This publication has 35 references indexed in Scilit:
- Bottle-feeding and the Risk of Pyloric StenosisPEDIATRICS, 2012
- Human metabolic individuality in biomedical and pharmaceutical researchNature, 2011
- The Danish National Patient RegisterScandinavian Journal of Public Health, 2011
- Infantile hypertrophic pyloric stenosis: genes and environmentArchives of Disease in Childhood, 2008
- Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human SerumPLoS Genetics, 2008
- Infantile hypertrophic pyloric stenosis: A comparative study of incidence and other epidemiological characteristics in seven European regionsThe Journal of Maternal-Fetal & Neonatal Medicine, 2008
- The Continuing Enigma of Pyloric Stenosis of InfancyEpidemiology, 2006
- Defective Cholesterol Biosynthesis Associated with the Smith-Lemli-Opitz SyndromeThe New England Journal of Medicine, 1994
- Sex differences in serum lipids and lipoproteins at birthEuropean Journal of Clinical Investigation, 1977
- Evidence that histidine is an essential amino acid in normal and chronically uremic man.JCI Insight, 1975