LVH [LV (left ventricular) hypertrophy] is an independent risk factor for CHD (coronary heart disease). During LVH, the preferred cardiac energy substrate switches from FAs (fatty acids) to glucose. LPL (lipoprotein lipase) is the key enzyme in triacylglycerol (triglyceride) hydrolysis and supplies FAs to the heart. To investigate whether substrate utilization influences cardiac growth and CHD risk, we examined the association between the functional LPL S447X (rs328) variant and hypertension-induced LV growth and CHD risk. LPL-X447 has been shown to be more hydrolytically efficient and would therefore release more free FAs than LPL-S477. In a cohort of 190 hypertensive subjects, LPL X447 was associated with a greater LV mass index [85.2 (1.7) in S/S compared with 91.1 (3.4) in S/X+X/X; P=0.01], but no such association was seen in normotensive controls (n=60). X447 allele frequency was higher in hypertensives with than those without LVH {0.14 [95% CI (confidence interval), 0.08–0.19] compared with 0.07 (95% CI, 0.05–0.10) respectively; odds ratio, 2.52 (95% CI, 1.17–5.40), P=0.02}. The association of LPL S447X with CHD risk was then examined in a prospective study of healthy middle-aged U.K. men (n=2716). In normotensive individuals, compared with S447 homozygotes, X447 carriers were protected from CHD risk [HR (hazard ratio), 0.48 (95% CI, 0.23–1.00); P=0.05], whereas, in the hypertensives, X447 carriers had increased risk [HR, 1.54 (95% CI, 1.13–2.09) for S/S (P=0.006) and 2.30 (95% CI, 1.53–3.45) for X447+ (P<0.0001)] and had a significant interaction with hypertension in CHD risk determination (P=0.007). In conclusion, hypertensive LPL X447 carriers have increased risk of LVH and CHD, suggesting that altered FA delivery constitutes a mechanism through which LVH and CHD are associated in hypertensive subjects.
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June 2007
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Research Article|
May 14 2007
The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease
Philippa J. Talmud;
*Centre for Cardiovascular Genetics, British Heart Foundation (BHF) Laboratories, The Rayne Building, Department of Medicine, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, U.K.
Correspondence: Professor Philippa J. Talmud (email [email protected]).
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David M. Flavell;
David M. Flavell
*Centre for Cardiovascular Genetics, British Heart Foundation (BHF) Laboratories, The Rayne Building, Department of Medicine, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, U.K.
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Khaled Alfakih;
Khaled Alfakih
†BHF Cardiac MRI Unit, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.
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Jackie A. Cooper;
Jackie A. Cooper
*Centre for Cardiovascular Genetics, British Heart Foundation (BHF) Laboratories, The Rayne Building, Department of Medicine, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, U.K.
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Anthony J. Balmforth;
Anthony J. Balmforth
‡BHF Heart Research Centre, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.
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Mohan Sivananthan;
Mohan Sivananthan
†BHF Cardiac MRI Unit, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.
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Hugh E. Montgomery;
Hugh E. Montgomery
*Centre for Cardiovascular Genetics, British Heart Foundation (BHF) Laboratories, The Rayne Building, Department of Medicine, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, U.K.
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Alistair S. Hall;
Alistair S. Hall
‡BHF Heart Research Centre, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.
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Steve E. Humphries
Steve E. Humphries
*Centre for Cardiovascular Genetics, British Heart Foundation (BHF) Laboratories, The Rayne Building, Department of Medicine, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, U.K.
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Publisher: Portland Press Ltd
Received:
December 01 2006
Revision Received:
January 29 2007
Accepted:
February 12 2007
Accepted Manuscript online:
February 12 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2007 The Biochemical Society
2007
Clin Sci (Lond) (2007) 112 (12): 617–624.
Article history
Received:
December 01 2006
Revision Received:
January 29 2007
Accepted:
February 12 2007
Accepted Manuscript online:
February 12 2007
Citation
Philippa J. Talmud, David M. Flavell, Khaled Alfakih, Jackie A. Cooper, Anthony J. Balmforth, Mohan Sivananthan, Hugh E. Montgomery, Alistair S. Hall, Steve E. Humphries; The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease. Clin Sci (Lond) 1 June 2007; 112 (12): 617–624. doi: https://doi.org/10.1042/CS20060344
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