Navegando por Autor "Wareham, Nick J."
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Item HMGCR gene polymorphism is associated with stroke risk in the EPIC-Norfolk study.(2010) Freitas, Renata Nascimento de; Khaw, Kay-Tee; Wu, Kelvin; Bowman, Richard; Jeffery, Hannah; Luben, Robert; Wareham, Nick J.; Rodwell, SheilaBackground Earlier, a G/T single nucleotide polymorphism (SNP) in the HMGCR gene was shown to significantly reduce the overall serum lipids response to pravastatin. This study aimed to investigate the relationship of the rs17238540 SNP with coronary heart disease, stroke and cardiovascular disease risk. Design Cross-sectional study from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. Methods Genotype was determined by pyrosequencing 23 011 participants, for whom clinical and biochemical data were available. Baseline risk factors according to genotype were evaluated, and the risk for fatal and nonfatal stroke, ischaemic heart disease and all types of cardiovascular diseases were assessed by logistic regression after approximately 11 years of follow-up. Results The G allele carriers presented 1.4 mmHg higher systolic blood pressure and 0.8 mmHg higher diastolic blood pressure than those who were TT carriers. They also presented higher risk of prevalent total (odds ratio: 1.44, 95% confidence interval: 1.05–1.97, P = 0.025) and nonfatal (odds ratio: 1.56, 95% confidence interval: 1.12–2.17, P = 0.009) stroke events compared with the TT individuals in the multivariate models. Conclusion An association between the rs17238540 SNP and stroke risk was observed, independent of the effect of the SNP on the blood pressure. The possible mechanisms involved, besides the effect on blood pressure, might be related to pleiotropic functions of the HMGCR, and remain to be explored.Item A HMGCR polymorphism is associated with relations between blood pressure and urinary sodium and potassium ratio in the Epic-Norfolk Study.(2009) Freitas, Renata Nascimento de; Khaw, Kay-Tee; Wu, Kelvin; Bowman, Richard; Jeffery, Hannah; Luben, Robert; Wareham, Nick J.; Bingham, Sheila A.A polymorphism in the HMGCR gene (rs17238540) was related to a lower response to pravastatin treatment and we aimed to investigate whether an interaction is present for this polymorphism on blood pressure (BP) and salt intake. Cross-sectional urinary sodium and potassium concentration and the polymorphism were assessed in a large population study. Participants with the mutated allele (G) had significantly higher BP than homozygous TT. There were highly significant positive trends between BP and urinary sodium:potassium ratio across quartiles in men, with less effect in women, especially women carrying the mutated allele, G. Multivariate regression showed a significant positive association between BP and the urinary sodium: potassium ratio that differed in men and women according to genotype. In men carrying the G allele, the regression slopes for diastolic BP and systolic BP were higher than in men TT and the opposite was observed in women. Our results suggest that the SNP rs17238540 in the HMGCR is associated with the BP response to urinary sodium: potassium ratio, the magnitude of the association differing according to possession of the G allele. JAm Soc Hypertens 2009;3(4):238–244.Item Relationship between plasma fibrinogen and fiber intake in the EPIC-Norfolk cohort.(2012) Freitas, Renata Nascimento de; Luben, Robert; Wareham, Nick J.; Kay-Tee, KhawItem A single nucleotide polymorphism in the 3-hydroxy-3-methylglutarylcoenzyme A reductase gene (HMGCR) influences the serum triacylglycerol relationship with dietary fat and fibre in the european prospective investigation into cancer and cutrition in Norfolk (EPIC-Norfolk) study.(2010) Freitas, Renata Nascimento de; Kay-Tee, Khaw; Wu, Kelvin; Bowman, Richard; Jeffery, Hannah; Luben, Robert; Wareham, Nick J.; Bingham, Sheila A.The objective of the present study was to investigate the influence of the single nucleotide polymorphism (rs17238540) at the 3-hydroxy-3-methylglutaryl- coenzyme A reductase gene (HMGCR) on the relationship between serum lipids and dietary fat and fibre (NSP). FFQ and pyrosequencing were used to assess cross-sectional dietary intake and HMGCR genotype in a population study with data for serum lipids available. Genotype frequencies and allele distributions for 23 011 participants were: TT 95·65 %, TG 4·29% and GG 0·06 %; T 97·8% and G 2·2 %. In regression analyses, the TG þ GG group showed a significant positive relationship between TAG and SFA intake (þ0·11 (95% CI 0·02, 0·20) mmol TAG/l; P¼0·017; per 3% SFA energy increase) while the TT individuals showed no change in the TAG levels related to SFA intake (20·0007 (95% CI 20·02, 0·02) mmol TAG/l; P¼0·99). TG þ GG individuals showed an inverse relationship between TAG and fibre intake higher (20·14 (95% CI 20·22, 20·05) mmol TAG/l than the TT group (20·04 (95% CI 20·06, 20·02) mmol TAG/l). In both cases the respective coefficient regressions of TAG were different between the genotype groups (Z ¼ 2·27, P¼0·023 for SFA intake; Z ¼ 2·19, P¼0·029 for fibre intake). Individuals carrying the G allele may show a greater response in lower TAG levels with reduced SFA intake and increased fibre intake compared with those homozygous for the T allele. The effectiveness of different dietary interventions to control serum lipids may vary according to HMGCR genotype.