Apolipoprotein AIMarburg: studies on two kindreds with a mutant of human apolipoprotein AI.

Three probands heterozygous for a mutant of apolipoprotein AI (apo AIMarburg, Utermann et al. 1982a) were detected by screening of 2282 unrelated individuals resulting an a frequency estimate of about 1/750 in the German population. All three probands with apo AIMarburg had hypertriglyceridemia (triglyceride above 250 mg/dl) and subnormal HDL-cholesterol (below 30 mg/dl), but no other lipoprotein abnormalities. The kindreds of two probands with AIMarburg were studied. The family data are consistent with an autosomal codominant inheritance of the trait. A total of 16 heterozygous blood relatives with the mutant AIMarburg were detected in these kindreds. Analysis of the plasma lipid and lipoprotein levels in relation to the apo AI phenotype was complicated by the high prevalence of diabetes mellitus and thyroid disease in one kindred and of hyperlipidemia in both kindreds. No consistent relationship between plasma lipid and lipoprotein levels, and the mutant apo AI could be demonstrated. Instead the mutant apo AI and the dyslipoproteinemia seem to co-exist independently in these kindreds. Three sibs with the homozygous apo E-2/2 phenotype were detected in one kindred, and all three sibs had subnormal LDL-cholesterol and beta-VLDL, e.g., the lipoprotein abnormality characterizing primary dysbetalipoproteinemia. Genetic apo E phenotypes and the apo AI mutant segregated independently, indicating that the structural gene loci for apo E and apo AI are not closely linked.