The common functional polymorphism -50G>T of the CYP2J2 gene is not associated with ischemic coronary and cerebrovascular events in an urban-based sample of Swedes.
BACKGROUND
CYP2J2 is responsible for the production of 5,6 8,9 11,12 and 14,15-epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. It is abundantly expressed in human heart and also present in kidney and vasculature. Carriers of a common polymorphism, the CYP2J2 -50G>T, rs890293, have reduced expression of CYP2J2 mRNA level in the heart putatively through the interference with a binding site for a transcription factor with consequently reduced circulating levels of CYP2J2 epoxygenase metabolites in vivo.


OBJECTIVE
The aim of the present study was to evaluate the effect of this functional polymorphism on blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes.


METHODS
The CYP2J2 polymorphism was genotyped in 5740 participants of the cardiovascular cohort of the 'Malmö Diet and Cancer' study. The incidence of cardiovascular events (coronary events, n = 261; ischemic stroke, n = 185) was monitored over 10 years of follow-up.


RESULTS
In the whole population the polymorphism had no effect on BP and hypertension prevalence and no interaction was found between the polymorphism and sex, age or body mass index. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke and coronary events was not significantly different in carriers of different genotypes.


CONCLUSIONS
Our data do not support a major role for the CYP2J2 -50G>T variant in determining BP level and incident ischemic events. Other studies are needed to elucidate if other polymorphisms in the same gene could have a role in BP homeostasis or incidence of cardiovascular events.
Department of Clinical Sciences, Lund University, University Hospital of Malmö, Sweden. cristiano.fava@med.lu.se
Cristiano
C
Fava
Martina
M
Montagnana
Peter
P
Almgren
Bo
B
Hedblad
Gunnar
G
Engström
Göran
G
Berglund
Pietro
P
Minuz
Olle
O
Melander
D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D014505:Urban Population
C000717350:CYP2J2 protein, human; D017931:DNA Primers; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2