INHERITANCE OF PLASMA APOLIPOPROTEIN-B LEVELS IN FAMILIES OF PATIENTS UNDERGOING CORONARY ARTERIOGRAPHY AT AN EARLY AGE

An elevated plasma level of apolipoprotein B (apoB), the major protein of low density lipoproteins, is a risk factor for coronary artery disease. This study tested the hypothesis, suggested by previous studies, that the apoB level is strongly influenced by a major gene. The study population included 832 family members of 1 16 subjects who had undergone elective coronary arteriography at an early age. The apoB level was adjusted for age, gender, body mass index, alcohol consumption, and cigarette smoking (R2 = 20%). ApoB levels revealed strong familial aggregation with correlations among spouses of 0.23, parent-offspring of 0.16, and siblings of 0.21. Regressive models were used to examine inter-individual variation in adjusted apoB levels. In the total sample, familial aggregation of the apoB level was consistent with two models: (1) a major gene model and (2) a polygenic model with a mixture of non-transmitted ''types.'' Comparison of these two models in each family showed that 57 families supported the first model over the second. Segregation analysis in these 57 families conclusively favored a major gene model with codominant transmission. Genotypic means were 124, 164, and 208 mg/dl with relative frequencies of 45%, 44%, and 11%. Linkage studies in these families can be used to clarify the molecular basis of apoB regulation. However, in the whole population the genetic control of apoB levels may be quite complex. (C) 1993 Wiley-Liss, Inc.