Ward Natalie C, Croft Kevin D, Puddey Ian B, Phillips Michael, van Bockxmeer Frank, Beilin Lawrence J, Barden Anne E
aUniversity of Western Australia, School of Medicine & Pharmacology, Royal Perth Hospital bSchool of Surgery and Pathology cWestern Australian Institute for Medical Research, University of Western Australia, Perth, Western Australia, Australia.
J Hypertens. 2014 Jul;32(7):1495-502; discussion 1502. doi: 10.1097/HJH.0000000000000208.
Genetic background partly determines the efficacy of interventions to lower blood pressure (BP). The CYP4F2 and CYP4A11 enzymes are renal 20-hydroxyeicosatetraenoic acid (20-HETE) synthases that regulate BP. Gene variants of CYP4F2 and CYP4A11 associate with hypertension and stroke. We showed that a gene variant of CYP4F2 but not CYP4A11 was associated with increased 20-HETE excretion and BP.
To compare BP and 20-HETE responses in carriers of the CYP4F2 1347G/A polymorphism and controls CYP4F2-GG (wildtype), during weight loss.
Volunteers genotyped as CYP4F2GA/AA (n = 26) and controls genotyped as CYP4F2 GG (n = 27) were counselled to reduce weight for 12 weeks, followed by 4 weeks of weight stabilization. Weight, 24-h BP, pulse pressure and urinary 20-HETE were measured at baseline, 12 and 16 weeks.
At baseline, SBP was (+1.7 mmHg, P = 0.047) in the CYP4F2 GA/AA genotype. Compared with baseline, weight fell by 3.9 kg, P = 0.0001, in both genotypes, and was maintained to 16 weeks. SBP fell by (-7.6 mmHg, P = 0.004) in both genotypes after 12 weeks. However, after weight stabilization, SBP was +3.6 mmHg, P = 0.004 in CYP4F2 GA/AA genotype. DBP and heart rate changed similarly over time. Pulse pressure fell with weight loss (P < 0.001), but was elevated in the CYP4F2 GA/AA genotype at all time-points (+3.1 mmHg, P < 0.001). Urinary 20-HETE was similar at baseline and 12 weeks but elevated in the CYP4F2 GA/AA genotype (P = 0.017) after weight stabilization.
Maintenance of lower BP after weight loss is more difficult for carriers of the CYP4F2 G1347A polymorphism and may be related to increased arterial stiffness and increased 20-HETE synthesis.
遗传背景部分决定了降低血压（BP）干预措施的疗效。细胞色素P450 4F2（CYP4F2）和细胞色素P450 4A11（CYP4A11）酶是调节血压的肾脏20-羟基二十碳四烯酸（20-HETE）合成酶。CYP4F2和CYP4A11的基因变异与高血压和中风相关。我们发现CYP4F2而非CYP4A11的基因变异与20-HETE排泄增加和血压升高有关。
比较细胞色素P450 4F2 1347G/A多态性携带者与细胞色素P4F2-GG（野生型）对照者在体重减轻期间的血压和20-HETE反应。
对基因分型为CYP4F2 GA/AA（n = 26）的志愿者和基因分型为CYP4F2 GG（n = 27）的对照者进行指导，使其减重12周，随后进行4周的体重稳定期。在基线、12周和16周时测量体重、24小时血压、脉压和尿20-HETE。
在基线时，CYP4F2 GA/AA基因型的收缩压为（+1.7 mmHg，P = 0.047）。与基线相比，两种基因型的体重均下降了3.9 kg，P = 0.0001，并维持到16周。12周后，两种基因型的收缩压均下降了（-7.6 mmHg，P = 0.004）。然而，体重稳定后，CYP4F2 GA/AA基因型的收缩压为+3.6 mmHg，P = 0.004。舒张压和心率随时间变化情况相似。脉压随体重减轻而下降（P < 0.001），但在所有时间点，CYP4F2 GA/AA基因型的脉压均升高（+3.1 mmHg，P < 0.001）。尿20-HETE在基线和12周时相似，但体重稳定后，CYP4F2 GA/AA基因型的尿20-HETE升高（P = 0.017）。
对于CYP4F2 G1347A多态性携带者而言，体重减轻后维持较低血压更为困难，这可能与动脉僵硬度增加和20-HETE合成增加有关。
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