Prevalence of alleles encoding defective lipoprotein lipase in hypertriglyceridemic patients of French Canadian descent.
It has previously been estimated that due to genetic "founder effects," 97% of lipoprotein lipase (LPL) gene alleles conferring type I hyperlipoproteinemia (HLP) in French Canadians encode one of the following mutant LPL forms: Gly188-->Glu, Pro207-->Leu, or Asp250-->Asn. Although the genetic basis of type I HLP is known to be homozygosity for LPL deficiency, that for other forms of HLP, especially types IV, and V HLP, is not clear. It is also unclear whether hypertriglyceridemia due to very low density lipoprotein (VLDL) overproduction can be distinguished phenotypically from that due to defective catabolism of plasma lipoprotein triglycerides. The present study took advantage of the unique circumstances inherent in the relatively genetically isolated French Canadian population to address these questions. This study was carried out in order to determine the prevalence of these three mutant LPL alleles, and of a fourth encoding LPL Asn291-->Ser, in French Canadian patients with hypertriglyceridemia. The prevalence of heterozygosity for one of the four LPL mutant alleles in nondiabetic, nonobese hypertriglyceridemic subjects was 16 of 95 type IV HLP (17%) and 4 of 26 type V HLP cases (15%). These alleles were not found in over 150 normotriglyceridemic subjects, supporting the likelihood that the mutant alleles were at least partially responsible for HLP. In addition, heterozygosity for LPL deficiency due to one of these mutations apparently did not contribute to hypoalphalipoproteinemia, and was observed in 3 of 39 subjects with type III HLP. The results suggest that in French Canadians, 15-20% of type IV and V HLP cases are associated with these genetic defects in plasma triglyceride catabolism.
Minnich
A
A
Clinical Research Institute of Montreal, P.Q., Canada.
Kessling
A
A
Roy
M
M
Giry
C
C
DeLangavant
G
G
Lavigne
J
J
Lussier-Cacan
S
S
Davignon
J
J
D000328:Adult; D000375:Aging; D000483:Alleles; D001057:Apolipoproteins E; D001483:Base Sequence; D002170:Canada; D005260:Female; D005602:France / Q000208:ethnology; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000201:enzymology / Q000235:genetics; D015228:Hypertriglyceridemia / Q000201:enzymology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D008071:Lipoprotein Lipase