S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies.
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.
Jensen
Majken K
MK
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. mkjensen@hsph.harvard.edu
Rimm
Eric B
EB
Rader
Daniel
D
Schmidt
Erik B
EB
Sørensen
Thorkild I A
TI
Vogel
Ulla
U
Overvad
Kim
K
Mukamal
Kenneth J
KJ
D050154:Adiposity; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D015438:Health Behavior; D006801:Humans; D008055:Lipids / Q000097:blood / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D008055:Lipids; D008071:Lipoprotein Lipase