Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension

Abstract

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.

Cytochrome P450 genetic variants and hypertension risk in South Indian population

“…[19][20][21][22] This is contradicting with the present study and the study done in African American population. 4 This probably may be due to differences in ethnicity, 12 which is an important factor attributed to clinical outcomes.…”

“…This is in accordance with previous studies. 4,19 However, similar studies in larger and different populations must be carried out to conclude the role of CYP genes in association with hypertension. …”

“…The multi-logistic regression odds ratio (OR) of CYP2J2*7, CYP2C8*2, CYP2C8*3, CYP2C9*2, CYP2C9*3 polymorphisms, and HTN compared between cases and healthy controls are shown in 19 However, they did not include CYP2C9 gene polymorphisms in their analysis. Further this study also showed no association between CYP2C8 and hypertension.…”

Hypertension, cardiovascular risk and polymorphisms in genes controlling the cytochrome P450 pathway of arachidonic acid: A sex-specific relation?

“…Interestingly, the variant allele was found to be protective in Caucasian men, but not in women [56]. In a Han Chinese population, despite no apparent effect for the functional variant CYP2J2*7 in the entire cohort, an association with hypertension and high systolic blood pressure was found in women homozygote for the T-allele of the intronic rs1155002 variant [68].…”

Emerging role of epoxyeicosatrienoic acids in coronary vascular function

“…A number of polymorphisms have been described at the human CYP2J2 locus, some of which encode variants with reduced catalytic activity [72,73], and at least one of which is independently associated with an increased risk of coronary artery disease [73]. A single-nucleotide polymorphism in the CYP2J2 gene is also associated with an increased risk of hypertension, particularly in Caucasians [74]. A number of polymorphisms in the human sEH gene have also been described [75,76].…”