Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in the families of NIDDM patients

Abstract

We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA1c 7.1 +/- 1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3-6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) nondiabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8 +/- 33.3 vs 22.3 +/- 19.5 mg/dl, p < 0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p < 0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p < 0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.

Associations Among Serum Lipoprotein(a) Levels, Apolipoprotein(a) Phenotypes, and Myocardial Infarction in Patients With Extremely Low and High Levels of Serum Lipoprotein(a)

“…Our finding that Lp(a) is an independent predictor for MI agrees with the results of most other recent studies, [14][15][16][17] except for 2 prospective studies. 18,19 Our finding that subjects with extremely high Lp(a) levels had small apo(a) isoforms and those with extremely low Lp(a) levels had large apo(a) isoforms confirms the findings of both our previous studies 11,12,32 and other studies 8,9,33 that an inverse relationship exists between apo(a) isoform size and plasma Lp(a) levels. Furthermore, this inverse relationship has been reported to be due to a difference in the rate of production, but not in the rate of catabolism, of Lp(a).…”

“…In the present study, we examined the associations among serum Lp(a) level, apo(a) isoform phenotype, and MI in subjects with extremely low and high Lp(a) levels, because such subjects may provide a better understanding of the effects of the interaction of serum Lp(a) levels and the apo(a) phenotype on the occurrence of MI. We excluded subjects with acute MI 23 and uncontrolled DM 12 which are known to affect Lp(a) levels. Our findings indicate that both Lp(a) and the apo(a) isoform phenotype are significantly associated with MI, independent of confounding risk factors, and that the apo(a) phenotype contributes to, but does not completely explain, the increased Lp(a) in patients with MI.…”

“…41,42 It has been reported that the apo(a) gene may account for more than 90% of the inter-individual difference within a pedigree, 10 a similar tendency to that reported by us. 12 However, the fact that increased Lp(a) levels in patients with MI can not be completely explained by differences in apo(a) isoform size suggest that other factors, such as the abnormalities of thrombosis or fibrinolysis due to increased Lp(a) or the vascular smooth muscle cell proliferation due to the inhibition of transforming growth factorb by Lp(a), 43 may be involved. Because only the interaction of Lp(a), apo(a) phenotype, and history of MI were assessed in the current study, such an analysis in acute coronary syndrome, including unstable angina pectoris, should be done in a future study.…”

“…An inverse relationship has been demonstrated between plasma Lp(a) concentrations and the size of apo(a), 8,11 and a smaller Lp(a) band was well correlated with Lp(a) levels in double-banded phenotypes. [11][12][13] High plasma levels of Lp(a) have been shown to be associated with myocardial infarction (MI), 14-17 although this association was not confirmed by 2 prospective studies. 18,19 Apo(a) size polymorphism has been shown to be inversely associated with the risk of coronary heart disease (CHD) in Jpn Circ J 1999; 63: 659 -665 (Received April 2, 1999; revised manuscript received May 24, 1999; accepted May 27, 1999 , age: 62±10 y) and control subjects (n=92, M/F: 53/39, age: 58±14 y) were classified into quintile groups (Groups I to V) according to Lp(a) levels.…”

“…Japanese Circulation Journal Vol.63, September 1999 patients with end-stage renal disease, 20 hypertension (HT) 21 or diabetes mellitus (DM), 12 those undergoing coronary bypass surgery, 22 and hemodialysis patients with or without DM. 13 However, the relation between apo(a) isoform size polymorphism and MI has rarely been studied, 23 and it would be interesting to determine whether, and how much, apo(a) isoform size polymorphism contributes to the increased serum Lp(a) levels in MI, because an inverse relation does exist between plasma Lp(a) levels and apo(a) size.…”