title: The functional variant V433M of the CYP4F2 and the metabolic syndrome in Swedes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden. cristiano.fava@med.lu.se
authors.forename: Cristiano
authors.initials: C
authors.lastname: Fava
authors.forename: Martina
authors.initials: M
authors.lastname: Montagnana
authors.forename: Elisa
authors.initials: E
authors.lastname: Danese
authors.forename: Marketa
authors.initials: M
authors.lastname: Sjögren
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Gian Cesare
authors.initials: GC
authors.lastname: Guidi
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Pietro
authors.initials: P
authors.lastname: Minuz
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D000328:Adult; D000368:Aged; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human