A common mutation in the lipoprotein lipase gene (N291S) alters the lipoprotein phenotype and risk for cardiovascular disease in patients with familial hypercholesterolemia.
BACKGROUND
Recently, a mutation in the lipoprotein lipase (LPL) gene (N291S) has been reported in 2% to 5% of individuals in western populations and is associated with increased triglyceride (TG) and reduced HDL cholesterol (HDLC) concentrations.


RESULTS
Here we report a significant alteration in biochemical and clinical phenotype in subjects with familial hypercholesterolemia (FH) who are heterozygous for this N291S LPL mutation. Sixty-four FH heterozygotes carrying the N291S mutation had significantly a higher TG level (P=.004), a higher ratio of total cholesterol to HDLC (P<.001), and lower HDLC concentrations (P=.002) compared with 175 FH heterozygotes without this LPL mutation. Moreover, the N291S mutation conferred a significantly greater risk for developing cardiovascular disease in FH heterozygotes compared with FH heterozygotes without this LPL mutation (odds ratio, 3.875; P=.006).


CONCLUSIONS
These data provide evidence that a common LPL variant (N291S) significantly influences the biochemical phenotype and risk for cardiovascular disease in patients with FH.
Wittekoek
M E
ME
Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
Pimstone
S N
SN
Reymer
P W
PW
Feuth
L
L
Botma
G J
GJ
Defesche
J C
JC
Prins
M
M
Hayden
M R
MR
Kastelein
J J
JJ
D000328:Adult; D000886:Anthropometry; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism; D003710:Demography; D005260:Female; D005787:Gene Frequency; D005796:Genes / Q000235:genetics*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D008071:Lipoprotein Lipase / Q000235:genetics*; D008074:Lipoproteins / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D015995:Prevalence; D012307:Risk Factors; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism
D008076:Cholesterol, HDL; D008074:Lipoproteins; D014280:Triglycerides; D008071:Lipoprotein Lipase