Contribution of apolipoprotein(a) size, pentanucleotide TTTTA repeat and C/T(+93) polymorphisms of the apo(a) gene to regulation of lipoprotein(a) plasma levels in a population of young European Caucasians.

Several studies indicate that the inter-individual variation in plasma concentrations of lipoprotein(a) (Lp(a)) is mainly under genetic control. To define the effect of three DNA polymorphisms on apolipoprotein(a) (apo(a)) expression, we have determined plasma Lp(a) concentrations, apo(a) isoform size, KpnI allele size, the TTTTA pentanucleotide repeat number in the 5' control region of the apo(a) gene and the +93 C/T polymorphism in a European Caucasian population. The simultaneous determination of the kringle 4 (K4) number by genotyping and by phenotyping revealed that the size distribution of non-expressed apo(a) alleles was markedly skewed towards alleles with greater than 25 K4 repeats. This is consistent with the inverse relationship frequently described between the kringle 4 number and the plasma Lp(a) level. Apportioning the Lp(a) concentration from the surface of the peaks on apo(a) phenotyping blots, we have observed that the Lp(a) plasma concentration associated with alleles having more than 25 K4 units does not exceed 400 mg/l, whereas the range of Lp(a) concentrations associated with smaller alleles was broad, from 0 to more than 1000 mg/l. It can thus be concluded that the number of K4 repeats is the main determinant of Lp(a) concentration when this number is more than 25, whereas other polymorphisms may be involved in the alleles with fewer than 26 K4. Analyses of the TTTTA repeat number and of the +93 C/T polymorphism were performed in subjects with KpnI alleles of the same length: low Lp(a) concentrations were shown to be preferentially associated with the presence of apo(a) alleles with more than eight pentanucleotide repeats while no association was revealed between Lp(a) plasma levels and the C/T polymorphism. These results demonstrate that the (TTTTA)(n) polymorphism affects the Lp(a) expression independently of apo(a) size polymorphism.

[Influence of alleles of apolipoprotein E on restenosis after coronary angioplasty in women]. / Influence des allèles de l'apolipoprotéine E sur la resténose après angioplastie coronaire chez la femme.

Although coronary stenting reduces the incidence of post-angioplasty restenosis, it remains a problem. The influence of lipoproteins on the development of atherosclerosis has been demonstrated but their role in restenosis is controversial. Contradictory results have been published on the subject of the influence of the APO E genotype. In an initial study, the authors showed a closer correlation between Lp (a) and coronary artery disease in women than in men. A sub-group of women who underwent angioplasty and whose lipid profile had been well established, was analysed with respect to APO E alleles. The 59 patients who underwent angioplasty included 35 single, 20 twin and 4 triple vessel diseases. Control coronary angiography was performed in 40 of these women. A telephonic interview was carried out between 12 and 22 months after dilatation on the whole population. The apolipoproteins A1, B, Lp (a) and Lp A1 were measured by immunological, turbidimetric or electroimmunological techniques. The APO E genotyping was performed with the Inno-Lipa kit. The results showed 18 angiographic restenoses (Group A), 20 coronary artery disease without restenosis (Group B), 41 without angiographic (20) or clinical (21) restenosis (Group C). In Group A, the Lp (a) was well above the threshold value of 0.30 g/l. The e4 allele was associated with the highest values of total and LDL cholesterol fractions. There was no significant difference between the APO E genotype of the different groups or with respect to the severity of lesions. The authors conclude that if the e4 is more commonly associated with high LDL-cholesterol and Lp (a), its role in the process of restenosis remains unproven. A greater number of patients is required and further studies are desirable to determine the inflammatory and/or immunological mechanisms through which APO E could influence restenosis.