APOLIPOPROTEIN(A) PHENOTYPES AND SERUM LIPOPROTEIN(A) LEVELS IN MAINTENANCE HEMODIALYSIS-PATIENTS WITH WITHOUT DIABETES-MELLITUS

We studied the quantitative and qualitative characteristics of lipopro tein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients (123 males, 29 females) undergoing maintenance hemodi alysis (HD) with or without diabetes mellitus (DM), in 101 patients wi th diabetes mellitus without hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88 females). Serum Lp(a) levels wer e significantly (P < 0.01) higher in patients than in controls (26.2 /- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD without DM, 27. 1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in controls , respectively). Apo(a) phenotyping was performed by a sensitive, high resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In no rmal controls, the molecular weights of apo(a) isoforms were inversely correlated with plasma Lp(a) levels, and the same tendency was found in patients who were undergoing hemodialysis and/or who had diabetes m ellitus. We assumed the differences in apo(a) phenotypes detectable wi th our method reflected consecutive differences in molecular weights o f apo(a). The results of an analysis of covariance and a least square means comparison indicated that the regression lines between serum Lp( a) levels [log Lp(a)] and apo(a) phenotypes in patient groups were sig nificantly (P < 0.01) elevated for every apo(a) phenotype, as compared to the regression line of the control group. Even after the low molec ular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was observed. However, no differences were observed between the patien t groups. The frequency distributions of serum Lp(a) levels in the pat ient groups were significantly different at every cut off point [10, 2 0, 30, 40, and 50 mg/dl of Lp(a)] from those in the control group, as assessed by chi square statistics. These data indicate that serum Lp(a ) levels are controlled by alleles at the apo(a) locus in patients und ergoing hemodialysis, as well as in patients with diabetes mellitus, b ut that increased Lp(a) levels in hemodialysis and diabetic patients a re not regulated by genes encoding low molecular weight of apo(a) isof orms.