Objective: Cytochrome (CYP) 4F2 isoform is a key metabolizing enzyme for the renal 20-hydroxyeicosatetraenoic acid (20-HETE), which, as an endogenous vasoconstrictor, may influence properties of the peripheral muscular arteries and arterioles. We, therefore, investigated the CYP4F2 polymorphisms in relation to arterial wave reflections, as measured by augmentation indexes (AIx) in Chinese.
Methods: We performed arterial measurements by SphygmoCor and genotyped three CYP4F2 polymorphisms (V433M, rs3093089, and rs3093098) by PCR-restriction fragment length polymorphism in 1421 participants enrolled in the JingNing Population study. A replication study for the V433M polymorphism was performed in 924 Chinese recruited from a workplace setting. Urinary 20-HETE concentration was determined by ELISA in a randomly selected subsample of 318 JingNing individuals.
Results: In spite of the fact that genetic associations were not significant (P ≥ 0.12) in all JingNing participants, there was significant (Pint ≤ 0.02) interaction of the V433M polymorphism with sex and pulse rate in relation to peripheral and central AIx. M433 allele carriers, compared with V433V homozygotes, had significantly greater peripheral (+5.0%, P = 0.0002) and central AIx (+3.2%, P = 0.001) in 693 men. The corresponding values were +2.7% (P = 0.04) and +1.9% (P = 0.04) in 490 individuals of the top tertile of pulse rate (≥ 76 beats/min), and were +4.0% (P = 0.02) and +3.3% (P = 0.02) in 315 replication participants with a pulse rate at least 76 beats/min. Urinary 20-HETE concentration was significantly higher (P = 0.002) in M433M (2.06 ng/ml) and V433M (1.13 ng/ml) individuals than in V433V homozygotes (0.98 ng/ml).
Conclusion: The CYP4F2 V433M polymorphism is associated with the size of arterial wave reflections in male Chinese, or individuals with a faster pulse rate.