The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss
Background: 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 s...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
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2014
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| Online Access: | http://hdl.handle.net/20.500.11937/38490 |
| _version_ | 1848755334378684416 |
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| author | Ward, Natalie Croft, K. Puddey, I. Phillips, M. van Bockxmeer, F. Beilin, L. Barden, A. |
| author_facet | Ward, Natalie Croft, K. Puddey, I. Phillips, M. van Bockxmeer, F. Beilin, L. Barden, A. |
| author_sort | Ward, Natalie |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Background: 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. Aim: To compare BP and 20-HETE responses in carriers of the CYP4F2 1347G/A polymorphism and controls CYP4F2-GG (wildtype), during weight loss. Methods: 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. Results: 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. Conclusion: 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. |
| first_indexed | 2025-11-14T08:54:39Z |
| format | Journal Article |
| id | curtin-20.500.11937-38490 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:54:39Z |
| publishDate | 2014 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-384902017-09-13T14:15:44Z The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss Ward, Natalie Croft, K. Puddey, I. Phillips, M. van Bockxmeer, F. Beilin, L. Barden, A. Background: 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. Aim: To compare BP and 20-HETE responses in carriers of the CYP4F2 1347G/A polymorphism and controls CYP4F2-GG (wildtype), during weight loss. Methods: 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. Results: 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. Conclusion: 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/38490 10.1097/HJH.0000000000000208 restricted |
| spellingShingle | Ward, Natalie Croft, K. Puddey, I. Phillips, M. van Bockxmeer, F. Beilin, L. Barden, A. The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss |
| title | The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss |
| title_full | The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss |
| title_fullStr | The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss |
| title_full_unstemmed | The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss |
| title_short | The effect of a single nucleotide polymorphismof the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss |
| title_sort | effect of a single nucleotide polymorphismof the cyp4f2 gene on blood pressure and 20-hydroxyeicosatetraenoic acidexcretion after weight loss |
| url | http://hdl.handle.net/20.500.11937/38490 |