The Prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension.
BACKGROUND
The cytochrome P450 (CYP) epoxygenase pathway produces arachidonic acid metabolites that are vasoactive, that affect renal sodium handling, and that have been proposed to play a mechanistic role in hypertension. Multiple single nucleotide polymorphisms (SNP) in CYP2C8, 2C9, 2J2 and soluble epoxide hydrolase (sEH) have been identified, many of which have altered functional activity in vitro. We performed a case-control study to determine the prevalence of epoxygenase-related SNP in African American individuals and to evaluate whether these SNP are associated with increased risk of hypertension.


METHODS
Normotensive African American individuals (N = 107) and African American patients with hypertension (N = 108) were recruited. DNA was extracted from a venous blood sample and genotyped for CYP2C8*2,*3, CYP2C9*2-*5,*8,*11, CYP2J2 *2-*7, L50L, R49S, V113M, N124S, sEH R287Q, and sEH 403Rins variant alleles by allelic discrimination using real-time polymerase chain reaction. Genotype and allele frequencies were calculated and associations with hypertension were estimated using unconditional logistic regression, adjusting for age and sex.


RESULTS
No association was found between any of the variant alleles and hypertension. We did find that only the CYP2C8*3and CYP2C9*2 alleles were in strong linkage disequilibrium in both the hypertensive and healthy African American groups, a finding that was reported previously in healthy individuals of white ethnicity.


CONCLUSIONS
These results suggest that these epoxygenase-related SNP are not associated with increased risk of hypertension in the African American population. There was significant linkage disequilibrium between CYP2C8*3 and CYP2C9*2 alleles that was not associated with hypertension.
Dreisbach
Albert W
AW
Divisions of Nephrology and Clinical Pharmacology, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. adreisb@tulane.edu
Japa
Shanker
S
Sigel
Aster
A
Parenti
Melissa B
MB
Hess
Arthur E
AE
Srinouanprachanh
Sengkeo L
SL
Rettie
Allan E
AE
Kim
Helen
H
Farin
Federico M
FM
Hamm
L Lee
LL
Lertora
Juan J L
JJ
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008145:Louisiana / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010105:Oxygenases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
C000717350:CYP2J2 protein, human; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D000090762:Cytochrome P-450 CYP2J2; D004851:Epoxide Hydrolases