Advanced

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

Fava, Cristiano LU ; Montagnana, Martina LU ; Danese, Elisa; Sjögren, Marketa LU ; Almgren, Peter LU ; Guidi, Gian Cesare; Hedblad, Bo LU ; Engström, Gunnar LU ; Minuz, Pietro and Melander, Olle LU (2012) In Prostaglandins & other Lipid Mediators 98(1-2). p.31-36
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Prostaglandins & other Lipid Mediators
volume
98
issue
1-2
pages
31 - 36
publisher
Elsevier
external identifiers
  • wos:000304733100005
  • pmid:22484021
  • scopus:84860721139
ISSN
1098-8823
DOI
10.1016/j.prostaglandins.2012.03.001
language
English
LU publication?
yes
id
3526561a-d202-4858-8ab9-c7236cce4640 (old id 2519709)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22484021?dopt=Abstract
date added to LUP
2012-05-06 14:43:45
date last changed
2017-03-19 04:21:49
@article{3526561a-d202-4858-8ab9-c7236cce4640,
  abstract     = {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. <br/><br>
<br/><br>
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. <br/><br>
<br/><br>
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. <br/><br>
<br/><br>
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.},
  author       = {Fava, Cristiano and Montagnana, Martina and Danese, Elisa and Sjögren, Marketa and Almgren, Peter and Guidi, Gian Cesare and Hedblad, Bo and Engström, Gunnar and Minuz, Pietro and Melander, Olle},
  issn         = {1098-8823},
  language     = {eng},
  number       = {1-2},
  pages        = {31--36},
  publisher    = {Elsevier},
  series       = {Prostaglandins & other Lipid Mediators},
  title        = {The functional variant V433M of the CYP4F2 and the metabolic syndrome in Swedes.},
  url          = {http://dx.doi.org/10.1016/j.prostaglandins.2012.03.001},
  volume       = {98},
  year         = {2012},
}