UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease

Talmud, PJ; Flavell, DM; Alfakih, K; Cooper, JA; Balmforth, AJ; Sivananthan, M; ... Humphries, SE; + view all (2007) The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease. CLIN SCI , 112 (11-12) 617 - 624. 10.1042/CS20060344.

Full text not available from this repository.

Abstract

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-5477. 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 CHID, suggesting that altered FA delivery constitutes a mechanism through which LVH and CHD are associated in hypertensive subjects.

Type:Article
Title:The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease
DOI:10.1042/CS20060344
Keywords:coronary heart disease, fatty acid, genetics, hypertrophy, hypertension, lipoprotein lipase (LPL), LPL S447X variant, PROLIFERATOR-ACTIVATED RECEPTOR, ISCHEMIC-HEART, INDEPENDENT PREDICTOR, PLASMA TRIGLYCERIDES, TRANSGENIC MICE, BLOOD-PRESSURE, RAT-HEART, METABOLISM, FRAMINGHAM, ATHEROSCLEROSIS
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Clinical Physiology
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

Archive Staff Only: edit this record