© 1998 American Heart Association, Inc.
Original Contributions |
Frequency of ApoB and ApoE Gene Mutations as Causes of Hypobetalipoproteinemia in the Framingham Offspring Population
From the Lipid Metabolism Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston (F.K.W., C.L., K.L.T., J.M.O., E.J.S.), and the Framingham Heart Study, Framingham (P.W.F.W.), Mass.
Correspondence to Francine K. Welty, Cardiovascular Division, Beth Israel Deaconess Medical Center, 1 Autumn St, 5th Floor, Boston, MA 02215. E-mail fwelty{at}bidmc.harvard.edu
Abstract—Hypobetalipoproteinemia
(HBLP) is characterized by plasma concentrations of apolipoprotein B
(apoB) and low density lipoprotein cholesterol (LDL-C)
below the fifth percentile. Some forms of HBLP have been shown to be
due to truncated forms of apoB-100. A total of 3873 subjects
participating in the Framingham Offspring Study had LDL-C levels
measured every 4 to 5 years throughout a 25-year period. Seventy-five
subjects were identified with persistent HBLP, defined as an LDL-C <70
mg/dL on at least 2 observations, for a prevalence of 1.9% in this
population. Compared with subjects with LDL- C 
70 mg/dL, subjects
with HBLP had significantly lower mean levels of total
cholesterol, LDL-C, triglyceride, and apoB;
higher levels of high density lipoprotein cholesterol; and
a higher prevalence of the E2/E3 genotype: 38.7% versus 10.9%
(P<0.001). Men with HBLP had a larger mean LDL particle
size than did men with an LDL- C 70 mg/dL. One individual had a
truncated apoB as a cause of HBLP, for a prevalence of 0.03%. Medical
causes of HBLP included 2 cases of Crohn's disease, 1 of
hemochromatosis, and 1 of hepatitis. Three subjects with HBLP developed
coronary heart disease, for an incidence of 4% compared with
5% in those with an LDL- C 70 mg/dL (P=NS). The
incidence of cancer was 8% in those with HBLP compared with 4% in
those with an LDL-C 70 mg/dL (P=0.21). In conclusion,
a truncated apoB was a rare cause of HBLP, whereas the E2/E3
genotype was a much more common cause. A large prospective
study is needed to evaluate the incidence of cancer and
atherosclerosis in subjects with HBLP.
Key Words: hypobetalipoproteinemia • apolipoproteins • coronary heart disease • LDL cholesterol • cancer
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