BACKGROUND: Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies. METHODS: The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Danish Diet, Cancer and Health (DCH) study, totaling 245, 258, and 962 cases, respectively. RESULTS: S447X carriers tended to have lower TG and higher HDL-C concentrations than noncarriers. The S447X variant was associated with a lower risk of CHD in the NHS; the association was weaker in the HPFS and not statistically significant in the DCH women and men. The pooled relative risk per minor allele was 0.74 (0.56-1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD risk were more pronounced in obese individuals in the NHS study, but this finding was not consistent across the studies. CONCLUSIONS: The LPL S447X variant tended to be associated with lower TG and higher HDL-C levels, and lower risk of CHD in all 3 cohorts. Lipoprotein lipase is an attractive target for clinical intervention, but studies are needed to clarify whether greater benefit from this variant may be conferred in some subgroups.
BACKGROUND:Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPLS447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies. METHODS: The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Danish Diet, Cancer and Health (DCH) study, totaling 245, 258, and 962 cases, respectively. RESULTS:S447X carriers tended to have lower TG and higher HDL-C concentrations than noncarriers. The S447X variant was associated with a lower risk of CHD in the NHS; the association was weaker in the HPFS and not statistically significant in the DCHwomen and men. The pooled relative risk per minor allele was 0.74 (0.56-1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD risk were more pronounced in obese individuals in the NHS study, but this finding was not consistent across the studies. CONCLUSIONS: The LPLS447X variant tended to be associated with lower TG and higher HDL-C levels, and lower risk of CHD in all 3 cohorts. Lipoprotein lipase is an attractive target for clinical intervention, but studies are needed to clarify whether greater benefit from this variant may be conferred in some subgroups.
Authors: E B Rimm; E L Giovannucci; W C Willett; G A Colditz; A Ascherio; B Rosner; M J Stampfer Journal: Lancet Date: 1991-08-24 Impact factor: 79.321
Authors: Bernard Keavney; Alison Palmer; Sarah Parish; Sarah Clark; Linda Youngman; John Danesh; Colin McKenzie; Marc Delépine; Mark Lathrop; Richard Peto; Rory Collins Journal: Int J Epidemiol Date: 2004-07-15 Impact factor: 7.196
Authors: Margaret E Brousseau; Allison L Goldkamp; Dorothea Collins; Serkalem Demissie; Allison C Connolly; L Adrienne Cupples; Jose M Ordovas; Hanna E Bloomfield; Sander J Robins; Ernst J Schaefer Journal: J Lipid Res Date: 2004-08-01 Impact factor: 5.922
Authors: M C Vohl; B Lamarche; S Moorjani; D Prud'homme; A Nadeau; C Bouchard; P J Lupien; J P Després Journal: Arterioscler Thromb Vasc Biol Date: 1995-05 Impact factor: 8.311
Authors: Ulla Vogel; Majken K Jensen; Karen Margrete Due; Eric B Rimm; Håkan Wallin; Michael R S Nielsen; Anne-Pernille T Pedersen; Anne Tjønneland; Kim Overvad Journal: Atherosclerosis Date: 2011-06-17 Impact factor: 5.162
Authors: Frederick E Dewey; Viktoria Gusarova; Richard L Dunbar; Colm O'Dushlaine; Claudia Schurmann; Omri Gottesman; Shane McCarthy; Cristopher V Van Hout; Shannon Bruse; Hayes M Dansky; Joseph B Leader; Michael F Murray; Marylyn D Ritchie; H Lester Kirchner; Lukas Habegger; Alex Lopez; John Penn; An Zhao; Weiping Shao; Neil Stahl; Andrew J Murphy; Sara Hamon; Aurelie Bouzelmat; Rick Zhang; Brad Shumel; Robert Pordy; Daniel Gipe; Gary A Herman; Wayne H H Sheu; I-Te Lee; Kae-Woei Liang; Xiuqing Guo; Jerome I Rotter; Yii-Der I Chen; William E Kraus; Svati H Shah; Scott Damrauer; Aeron Small; Daniel J Rader; Anders Berg Wulff; Børge G Nordestgaard; Anne Tybjærg-Hansen; Anita M van den Hoek; Hans M G Princen; David H Ledbetter; David J Carey; John D Overton; Jeffrey G Reid; William J Sasiela; Poulabi Banerjee; Alan R Shuldiner; Ingrid B Borecki; Tanya M Teslovich; George D Yancopoulos; Scott J Mellis; Jesper Gromada; Aris Baras Journal: N Engl J Med Date: 2017-05-24 Impact factor: 91.245
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Authors: Amit V Khera; Hong-Hee Won; Gina M Peloso; Colm O'Dushlaine; Dajiang Liu; Nathan O Stitziel; Pradeep Natarajan; Akihiro Nomura; Connor A Emdin; Namrata Gupta; Ingrid B Borecki; Rosanna Asselta; Stefano Duga; Piera Angelica Merlini; Adolfo Correa; Thorsten Kessler; James G Wilson; Matthew J Bown; Alistair S Hall; Peter S Braund; David J Carey; Michael F Murray; H Lester Kirchner; Joseph B Leader; Daniel R Lavage; J Neil Manus; Dustin N Hartzel; Nilesh J Samani; Heribert Schunkert; Jaume Marrugat; Roberto Elosua; Ruth McPherson; Martin Farrall; Hugh Watkins; Eric S Lander; Daniel J Rader; John Danesh; Diego Ardissino; Stacey Gabriel; Cristen Willer; Gonçalo R Abecasis; Danish Saleheen; Frederick E Dewey; Sekar Kathiresan Journal: JAMA Date: 2017-03-07 Impact factor: 56.272
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