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Olle Melander

Principal investigator

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The functional variant V433M of the CYP4F2 and the metabolic syndrome in Swedes.

Author

  • Cristiano Fava
  • Martina Montagnana
  • Elisa Danese
  • Marketa Sjögren
  • Peter Almgren
  • Gian Cesare Guidi
  • Bo Hedblad
  • Gunnar Engström
  • Pietro Minuz
  • Olle Melander

Summary, in English

BACKGROUND AND AIM: The genetic basis of Metabolic syndrome (MetS) is largely unknown but a link with salt sensitivity is recognized. The cytochrome P450 isoform 4F2 (CYP4F2) is involved in renal production of 20-hydroxyeicosatethraenoic acid (20-HETE), a natriuretic substance associated with salt sensitivity. The same enzyme is implicated in ω-hydroxylation of very long and medium chain fatty acids in the liver suggesting its possible influence on gluco-metabolic components of MetS. The aim of the present study was to evaluate the effect of CYP4F2 V433M, a functional polymorphism previously associated with hypertension via renal salt reabsorption, on the individual components of MetS and MetS itself.



METHODS: The polymorphism was genotyped in the cardiovascular cohort of the Malmö Diet and Cancer (MDC-CVA) study and successively in the Malmö Preventive Project (MPP) cohort. Different definitions of the MetS were applied.



RESULTS: In the MDC-CVA, male, but not female, CYP4F2 M433 carriers had significantly higher levels of waist, triglycerides, BP and a composite sum of MetS phenotypes (MetS score) beside lower HDL-cholesterol respect to V-homozygotes. MetS, as defined in the ATPIII and the AHA/NHLBI definitions, was more prevalent in M-carriers with respect to V-homozygotes. In the MPP cohort, significant association was detectable only for triglycerides at baseline and for Diastolic BP at reinvestigation in male M-carriers.



CONCLUSION: The initial positive association of the CYP4F2 V433M polymorphism with components of MetS and MetS itself, found in MDC-CVA, was partially denied in another large cohort. The first association either could be due to a false positive result or alternatively, different genetic background or population stratification could have hidden the effect of the polymorphism in the replication cohort.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2012

Language

English

Pages

31-36

Publication/Series

Prostaglandins & other Lipid Mediators

Volume

98

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension
  • Cardiovascular Research - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1098-8823