title: Frequency of ApoB and ApoE gene mutations as causes of hypobetalipoproteinemia in the framingham offspring population.
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.
authors.affiliation: Lipid Metabolism Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. fwelty@bidmc.harvard.edu
authors.forename: F K
authors.initials: FK
authors.lastname: Welty
authors.forename: C
authors.initials: C
authors.lastname: Lahoz
authors.forename: K L
authors.initials: KL
authors.lastname: Tucker
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: P W
authors.initials: PW
authors.lastname: Wilson
authors.forename: E J
authors.initials: EJ
authors.lastname: Schaefer
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005828:Genetics, Population; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000737:chemistry; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology / Q000401:mortality; D010316:Particle Size; D015995:Prevalence
chemical_list: D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008077:Lipoproteins, LDL