JOURNAL ARTICLE
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
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Lipoproteins in familial hyperalphalipoproteinemia.

Familial hyperalphalipoproteinemia is determined by a major gene and is characterized by high levels of high density lipoprotein cholesterol and longevity. To describe the plasma lipoproteins in this condition more completely, a kindred consisting of the proband, her affected father, add her two affected brothers was studied. Fasting plasmas were analyzed for lipoprotein lipids by combined preparative ultracentrifugal and precipitation methods. Levels of apolipoprotein A-1 and apolipoprotein A-11, the major apoproteins of high density lipoproteins, were assayed by radioimmunoassay. The flotation properties of very low density, low density and high density lipoprotein were determined by zonal ultracentrifugation, and the isolated high density lipoprotein subfractions were characterized according to their lipid and apoprotein compositions. Total cholesterol of all subjects was normal, but triglycerides were elevated (above the 90th percentile) in the two brothers. High density lipoprotein cholesterol ranged from 150 to 165 mg/dl in the proband and from 72 to 89 mg/dl in her relatives. Apolipoprotein A-1 was 318 mg/dl in the proband and 156 to 169 mg/dl in the siblings; respective apolipoprotein A-11 values were 67 and 82 to 83 mg/dl. The high density lipoprotein cholesterol and apolipoprotein A-1 and A-11 values for the relatives are above the 95th percentile for sex and age, while the levels of the proband are the highest recorded in our laboratories. On zonal ultracentrifugation, very low density lipoprotein and low density lipoprotein had normal flotation properties. High density lipoprotein was divisible into three populations, HDL2, HDL3L, and HDL3D (Sf(1,21,26 degrees C), 59, 2.9, and 1.7 respectively), each of which floated in its usual position. But HDL2 was grossly elevated, accounting for most of the rise in the high density lipoprotein fraction. The compositions of the high density lipoprotein fractions with respect to the major lipid and apoprotein classes did not differ from normal. Thus, in this kindred, high density lipoprotein was quantitatively rather than qualitatively unusual. It is of interest that hypertriglyceridemia and hyperalphalipoproteinemia coexisted in the siblings. These concurrent elevations differ from the expected reciprocal relationship between high density lipoprotein and very low density lipoprotein levels in plasma, and suggests that in some subject the two abnormalities may be independently transmitted.

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