Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude Cas Témoin sur l'Infarctus du Myocarde.
Several lipoprotein lipase (LPL) gene polymorphisms have been found associated with fasting lipid levels, but their impact on coronary heart disease (CHD) is less clearly established. We investigated associations of LPL polymorphisms (HindIII, PvuII, Ser447-->Ter) and the newly described mutation Asn291-->Ser with the risk of myocardial infarction (MI), severity of atherosclerosis, and fasting plasma lipoprotein concentrations in the ECTIM study (614 patients and 733 controls). The Ter447 allele had a lowering effect on triglycerides (P < 0.01), VLDL-cholesterol (P < 0.05), apoC-III (P < 0.001), LpE:B (P < 0.01), and LpCIII:B (P < 0.05), and a raising effect on apoA-I levels (P < 0.05). The H- allele of the HindIII polymorphism was associated with lower apoC-III (P < 0.01) and higher HDL-cholesterol (P < 0.05) levels. The PvuII and Asn291-->Ser polymorphisms did not exhibit any significant association with the biochemical traits examined. The HindIII genotype distributions differed between cases and controls, the odds ratios for MI associated with H+H+ and H+H- genotypes being 2.05 (P < 0.01) and 1.74 (P < 0.05) by reference to H-H-. The lack of association between Ser447-->Ter and MI suggested that this mutation was unlikely to be the cause of the association found with HindIII. In some cases, the severity of atherosclerosis assessed by coronarography increased with the presence of P+ allele (coronary scores: 1.41, 1.57, and 1.64 in P-P-, P-P+, and P+P+ individuals respectively, P < 0.05). A similar trend on the coronary score was observed with the presence of the Asn291-->Ser mutation (1.58 vs. 1.90, P = 0.06). Our results suggest that the LPL gene is involved in the determination of lipoprotein profiles, the predisposition to CHD, and the severity of atherosclerosis.
Jemaa
R
R
INSERM U286, Faculté de Médecine Xavier Bichat, Paris, France.
Fumeron
F
F
Poirier
O
O
Lecerf
L
L
Evans
A
A
Arveiler
D
D
Luc
G
G
Cambou
J P
JP
Bard
J M
JM
Fruchart
J C
JC
D000328:Adult; D001216:Asparagine / Q000737:chemistry; D001483:Base Sequence; D016022:Case-Control Studies; D015247:Deoxyribonuclease HindIII; D015252:Deoxyribonucleases, Type II Site-Specific; D005602:France; D006801:Humans; D015810:Linkage Disequilibrium; D008071:Lipoprotein Lipase / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D009660:Northern Ireland; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012694:Serine / Q000737:chemistry
D008074:Lipoproteins; D012694:Serine; D001216:Asparagine; D008071:Lipoprotein Lipase; D015247:Deoxyribonuclease HindIII; C025630:CAGCTG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific