title: Relationship between salivary/pancreatic amylase and body mass index: a systems biology approach.
abstract: Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach.
  
  
  
  We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D.E.S.I.R. longitudinal study. The effect of the number of copies of AMY1A (encoding AMY1) or AMY2A (encoding AMY2) measured through droplet digital PCR was then analyzed on the same parameters in the same study. A Mendelian randomization analysis was also performed. We subsequently assessed the association between AMY1A copy number and obesity risk in two case-control studies (5000 samples in total). Finally, we assessed the association between body mass index (BMI)-related plasma metabolites and AMY1 or AMY2 activity.
  
  
  
  We evidenced strong associations between AMY1 or AMY2 activity and lower BMI. However, we found a modest contribution of AMY1A copy number to lower BMI. Mendelian randomization identified a causal negative effect of BMI on AMY1 and AMY2 activities. Yet, we also found a significant negative contribution of AMY1 activity at baseline to the change in BMI during the 9-year follow-up, and a significant contribution of AMY1A copy number to lower obesity risk in children, suggesting a bidirectional relationship between AMY1 activity and adiposity. Metabonomics identified a BMI-independent association between AMY1 activity and lactate, a product of complex carbohydrate fermentation.
  
  
  
  These findings provide new insights into the involvement of amylase in adiposity and starch metabolism.
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France. amelie.bonnefond@inserm.fr.
authors.forename: Amélie
authors.initials: A
authors.lastname: Bonnefond
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France.|Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4067, Australia.
authors.forename: Loïc
authors.initials: L
authors.lastname: Yengo
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dechaume
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Canouil
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Castelain
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Roger
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Allegaert
authors.affiliation: University of Lille, Inserm, U1190 - EGID, Lille, 59000, France.|Endocrine Surgery Department, CHU of Lille, Lille, 59000, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Caiazzo
authors.affiliation: University of Lille, Inserm, U1190 - EGID, Lille, 59000, France.|Endocrine Surgery Department, CHU of Lille, Lille, 59000, France.
authors.forename: Violeta
authors.initials: V
authors.lastname: Raverdy
authors.affiliation: University of Lille, Inserm, U1190 - EGID, Lille, 59000, France.|Endocrine Surgery Department, CHU of Lille, Lille, 59000, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Pigeyre
authors.affiliation: Qatar Biomedical Research Institute, Qatar Foundation, Doha, 5825, Qatar.
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Arredouani
authors.affiliation: Fleurbaix-Laventie Association, Laventie, 62840, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Borys
authors.affiliation: Inserm CIE 05 - Department of Clinical Epidemiology, Robert Debré Hospital, Paris, 75019, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lévy-Marchal
authors.affiliation: Pediatric Endocrine Department, CHU of Lille, Lille, 59000, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.affiliation: Inserm, U1138, Centre de Recherche des Cordeliers, Paris, 75006, France.|Paris-Diderot University, Sorbonne Paris-Cité, Paris, 75013, France.|Department of Endocrinology-Diabetology and Nutrition, DHU-FIRE, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Paris, 75018, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.affiliation: Inserm, U1018, CESP, Team 5 (EpReC, Renal and cardiovascular Epidemiology), UVSQ-UPS, Villejuif, 94807, France.
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.affiliation: Inserm, U1138, Centre de Recherche des Cordeliers, Paris, 75006, France.|Paris-Diderot University, Sorbonne Paris-Cité, Paris, 75013, France.|Department of Endocrinology-Diabetology and Nutrition, DHU-FIRE, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Paris, 75018, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.affiliation: University of Lille, Inserm, U1190 - EGID, Lille, 59000, France.|Endocrine Surgery Department, CHU of Lille, Lille, 59000, France.
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.affiliation: UF8832 - Biochimie Automatisée, Pôle de Biologie Pathologie Génétique, CHU of Lille, Lille, 59000, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Brousseau
authors.affiliation: University of Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, 59000, France. froguel@good.ibl.fr.|Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK. froguel@good.ibl.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D015992:Body Mass Index; D002648:Child; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009765:Obesity / Q000201:enzymology*; D055292:Pancreatic alpha-Amylases / Q000378:metabolism*; D055291:Salivary alpha-Amylases / Q000378:metabolism*; D049490:Systems Biology
chemical_list: C524788:AMY1A protein, human; C513534:AMY2A protein, human; D055292:Pancreatic alpha-Amylases; D055291:Salivary alpha-Amylases
keywords: AMY1A/AMY2A; Body mass index; Copy number variant; Mendelian randomization; Metabonomics; Obesity; Salivary/Pancreatic amylase; Starch