title: Sex-specific vitamin D effects on blood coagulation among overweight adults.
abstract: BACKGROUND
  Overweight adults are at increased risk for cardiovascular disease and vitamin D deficiency, whereas an important feature to vitamin D physiology is its sex dependence. The aim of this study was to examine whether vitamin D status improvement exerts a sexually dimorphic effect on serum proteins associated with cardiovascular risk among overweight adults.
  
  
  METHODS
  Unprocessed serum from age- and BMI-matched men (n = 26) and premenopausal women (n = 24) with vitamin D deficiency and after they achieved sufficiency through a 12-month nutritional intervention was analysed using our previously published depletion-free quantitative proteomics method. Key findings were verified with ELISA. Differentially expressed proteins were subjected to in silico bioinformatics assessment using principal component analysis, hierarchical clustering and Metacore™pathway analysis. All mass spectrometry proteomic data are available via ProteomeXchange (identifier: PXD003663).
  
  
  RESULTS
  A total of 282 proteins were differentially expressed after the intervention between men and women (P-value ≤ 0·05), in which the blood coagulation pathway was significantly enriched. In agreement with the proteomics findings, ELISA measurements showed vitamin K-dependent protein C, von Willebrand factor, fibrinogen gamma chain and multimerin-1 proteins, of relevance to blood coagulation, to be differentially affected (P-value ≤ 0·05) between sexes after vitamin D status correction.
  
  
  CONCLUSIONS
  This study identified novel protein-level molecular indicators on the sexually dimorphic effect of vitamin D status correction associated with blood coagulation among overweight adults. These sex-mediated vitamin D effects should be factored in the design and interpretation of vitamin D observational and interventional studies testing cardiometabolic outcomes.
authors.affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.|Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Al-Daghri
authors.affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.|Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Majed S
authors.initials: MS
authors.lastname: Alokail
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.|Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, Southampton, UK.
authors.forename: Antigoni
authors.initials: A
authors.lastname: Manousopoulou
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Heinson
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Attas
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Al-Saleh
authors.affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.|Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Shaun
authors.initials: S
authors.lastname: Sabico
authors.affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.|Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sobhy
authors.initials: S
authors.lastname: Yakout
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Woelk
authors.affiliation: First Department of Pediatrics, University of Athens, Athens, Greece.
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.|Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, Southampton, UK.|Cancer Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton, UK.
authors.forename: Spiros D
authors.initials: SD
authors.lastname: Garbis
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D003198:Computer Simulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D050177:Overweight / Q000150:complications / Q000378:metabolism*; D025341:Principal Component Analysis; D011486:Protein C / Q000378:metabolism*; D040901:Proteomics; D012737:Sex Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000150:complications / Q000178:diet therapy / Q000378:metabolism*; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D011486:Protein C; C027539:fibrinopeptides gamma; C069282:multimerin; D014841:von Willebrand Factor; D014807:Vitamin D; D005340:Fibrinogen; C104450:25-hydroxyvitamin D
keywords: Blood coagulation; serum proteomics; sexual dimorphism; vitamin D