Significant impact of the highly informative (CA)n repeat polymorphism of the APOA-II gene on the plasma APOA-II concentrations and HDL subfractions: The ECTIM study.
High density lipoproteins (HDL) are heterogeneous in their apolipoprotein composition and the role of apolipoprotein A-II (APOA-II) in HDL structure and metabolism is poorly understood. Yet, studies of naturally occurring variations of APOA-II in mice and experiments in transgenic mice overexpressing the APOA-II gene (APOA-II) have shown that APOA-II expression influences APOA-II plasma levels and HDL size and composition. In humans, two RFLPs (BstNI and MspI) have been described in the APOA-II gene. These RFLPs, however, have been inconstantly associated with variations in APOA-II plasma levels. In particular, the large multicentric ECTIM Study did not show any significant effect of the two RFLPs. Other polymorphisms consisting of repetitive sequences have been proposed as more informative markers than RFLPs. Thus, data from the ECTIM Study were reconsidered by integrating the additional information obtained from a highly informative multiallelic (CA)(n)-repeat polymorphism located in the second intron of the gene. The population study was composed of 763 non-treated male controls and 594 cases of myocardial infarction. In controls, the (CA)(19) allele was associated with significantly decreased APOA-II (P < 0.0009) and LpA-II:A-I (P < 0.02) plasma levels. Although the APOA-I plasma levels were not affected by the polymorphism, the (CA)(19) allele was associated with an increased LpA-I/LpA-II:A-I ratio (P < 0.004). No effect, however, could be detected on myocardial infarction. Study of the linkage disequilibrium and the estimation of haplotype frequencies indicated that the impact of the APOA-II locus could hardly be detected by using the BstNI and MspI RFLPs. These data revive interest in evaluating the role of the APOA-II locus in the control of APOA-II plasma levels and HDL composition.
INSERM Unité 508, Institut Pasteur de Lille, Lille, France.
Thierry
T
Brousseau
Anne-Marie
AM
Dupuy-Gorce
Alun
A
Evans
Dominique
D
Arveiler
Jean-Bernard
JB
Ruidavets
Bernadette
B
Haas
Jean-Pierre
JP
Cambou
Gérald
G
Luc
Pierre
P
Ducimetière
Philippe
P
Amouyel
Nicole
N
Helbecque
D000328:Adult; D000483:Alleles; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics*; D018900:Dinucleotide Repeats / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D016633:Apolipoprotein A-II