Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension.
CYP2J2 and CYP2C8 metabolize arachidonic acid (AA) to cis-epoxyeicosatrienoic acids (EETs), which play a central role in regulating renal tubular fluid-electrolyte transport and vascular tone. We hypothesized that functionally relevant polymorphisms in the CYP2J2 or CYP2C8 genes influence hypertension risk. We examined associations between CYP2J2*7 (G-50 T promoter) and CYP2C8*3 (Arg139Lys and Lys399Arg, which are in 100% linkage disequilibrium) polymorphisms and hypertension in a biethnic population from Tennessee. CYP2J2*7 variant allele frequency was significantly higher in African-Americans versus Caucasians (14.1% versus 7.7%, P=0.01), irrespective of hypertension status. When analysed separately by race, the genotype distribution of the CYP2J2*7 variant allele was not significantly different among African-Americans with/without hypertension, but was significantly different among Caucasians with/without hypertension (P=0.03). Indeed, the odds ratio of having hypertension attributable to carrying the CYP2J2*7 variant allele adjusted for age, gender, body mass index and family history was 0.39 (95% confidence interval 0.17-0.89) among Caucasians, suggesting a protective effect. Additional subgroup analyses revealed a significantly lower CYP2J2*7 variant allele frequency in hypertensive versus normotensive Caucasian males (5.6% versus 12.5%, P=0.02) and in hypertensive versus normotensive Caucasians without a family history of hypertension (1.5% versus 11.0%, P=0.03). With respect to the CYP2C8*3 variant, genotype distribution and allele frequencies were similar between normotensive and hypertensive subjects. This study provides evidence for an association between CYP2J2*7 genotype and hypertension in Caucasian males and Caucasians without a family history of hypertension, but suggests no association between CYP2C8*3 genotype and hypertension. Confirmation of these findings in additional populations is warranted.
King
Lorraine M
LM
Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Gainer
James V
JV
David
Gloria L
GL
Dai
Ding
D
Goldstein
Joyce A
JA
Brown
Nancy J
NJ
Zeldin
Darryl C
DC
D000328:Adult; D000483:Alleles; D001120:Arginine / Q000737:chemistry; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065727:Cytochrome P-450 CYP2C8; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004573:Electrolytes; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008239:Lysine / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010105:Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012737:Sex Factors
C000717350:CYP2J2 protein, human; D004573:Electrolytes; D003577:Cytochrome P-450 Enzyme System; D001120:Arginine; D010105:Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D000090762:Cytochrome P-450 CYP2J2; D008239:Lysine