Genetic variation at the lipoprotein lipase locus and plasma lipoprotein and insulin levels in the Québec Family Study.
The associations between the S447X, BamHI, HindIII and PvuII DNA variants of the lipoprotein lipase (LPL) gene and indicators of body fat, fat distribution and plasma lipids and insulin were studied in the Québec Family Study cohort. Strong linkage disequilibrium among all the markers was observed. For the S447X polymorphism, plasma very low density lipoprotein (VLDL)-cholesterol (chol) (P<0.001), total triglyceride (TG) (P=0.033) and VLDL-TG (P<0.001) levels were lower and high density lipoprotein (HDL)-chol level higher (P<0.001) in the subjects homozygous or heterozygous for X447 (X447+, n=160) compared to the homozygotes for the S447 allele (X447-, n=576). The BamHI, PvuII and HindIII polymorphisms were not associated with the plasma lipid values when all X447 allele carriers were removed. In addition, the HindIII polymorphism as well as the HindIII and S447X markers combination influenced the insulin area under the curve during an oral glucose tolerance test. We conclude that DNA sequence variation in the LPL gene contributes significantly to the variability in the levels of VLDL-chol, total- and VLDL-TG as well as HDL-chol. The effects of the other polymorphisms considered here are most likely mediated by their linkage disequilibrium with the S447X mutation. In addition, genetic variation at the LPL locus may, by an unknown mechanism, influence insulin metabolism but not body fat variability.
Ukkola
O
O
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Garenc
C
C
Pérusse
L
L
Bergeron
J
J
Després
J P
JP
Rao
D C
DC
Bouchard
C
C
D000328:Adult; D000466:Alkadienes; D015992:Body Mass Index; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood
D000466:Alkadienes; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D007328:Insulin; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; C025947:propadiene; D008071:Lipoprotein Lipase