title: Variation in the lipoprotein lipase gene influences exercise-induced left ventricular growth.
abstract: The adult heart relies predominantly on fatty acids (FA) for energy generation, and defects in FA catabolism cause dramatic left ventricular (LV) growth in early age. Since lipoprotein lipase (LPL) is the key enzyme in plasma triglyceride catabolism and is highly expressed in the myocardium, we investigated an association between the functional LPL gene serine 447 stop (S447X) variant and exercise-induced LV growth. The S447X variant was genotyped in 146 British Army recruits undergoing a 10-week exercise programme. Over the training period, X447 allele carriers showed less LV growth than S447 homozygotes (SS, 5.8+/-0.7%; SX, 2.2+/-1.5%; P=0.03) and a decrease in systolic blood pressure (DeltaSBP: SS, 1.9+/-1.3 mmHg; SX, -5.7+/-2.2 mmHg; P=0.015). Although LPL genotype did not significantly predict LV growth with DeltaSBP in statistical modelling (LPL, P=0.14; DeltaSBP, P=0.06), regression analysis indicated that LPL S447X genotype effect on DeltaSBP accounted for only 20% of the effect on LV growth. In multivariate analysis, LPL, peroxisome-proliferator-activated receptor alpha and angiotensin-converting enzyme genotypes were independent predictors of cardiac growth. Thus, LPL S447X genotype influenced exercise-induced changes in LV mass and SBP. Change in blood pressure accounted for a proportion of LV growth. These data suggest that increased myocardial FA availability may reduce exercise-induced LV growth.
authors.affiliation: Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, University College London, London, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Flavell
authors.forename: Peter T E
authors.initials: PT
authors.lastname: Wootton
authors.forename: Saul G
authors.initials: SG
authors.lastname: Myerson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: World
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D015444:Exercise; D014644:Genetic Variation; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008889:Military Personnel; D012016:Reference Values
chemical_list: D008071:Lipoprotein Lipase; D019808:Losartan