Abstract
Two novel, distinct truncated forms of apolipoprotein B (apo B) designated as apo B-90 and apo B-40 were found in five members of a kindred with hypobetalipoproteinemia. Sodium dodecyl sulfate gels and immunoblots of plasma or low density lipoprotein (LDL) (d = 1.019 to 1.063 g/ml) of the affected members demonstrated the presence of one or both of the truncated apo B bands. Employing four monoclonal anti-LDL antibodies with defined regional specificities, we demonstrated that amino terminal epitopes of the truncated apo Bs were intact, but that 10% and 60%, respectively, of the carboxyl terminal regions were absent. Thrombin digestion of apo B-90 generated an abnormally small T2 fragment, confirming that approximately 550 amino acids had been deleted from the carboxyl terminus of apo B-100. Restriction fragment length polymorphism analysis and variable number of tandem repeat typing of the 3' flanking hypervariable region of the apo B gene made it possible to distinguish all four parenteral alleles and therefore to follow the inheritance of the apo B variants through the family. This pedigree analysis confirmed the inheritance of the apo B-90 and apo B-40 identified by monoclonal antibody binding studies. Siblings heterozygous for apo B-90 or apo B-40 exhibited > 65% lower concentrations of apo B-90 or apo B-40 relative to apo B-100 and had 5th percentile LDL cholesterol concentrations. Compound heterozygotes (apo B-90/apo B-40) had the lowest LDL levels, and their LDL particles were small in size. The LDL of compound heterozygotes interacted with LDL receptors of cultured fibroblasts with greater than normal affinity, suggesting that the low level of apo B-90 in plasma may have been due to rapid clearance. The reasons for the low levels of apo B-40 are not known.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 856-868 |
| Number of pages | 13 |
| Journal | Arteriosclerosis |
| Volume | 9 |
| Issue number | 6 |
| State | Published - 1989 |
| Externally published | Yes |
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Keywords
- apoprotein B
- hypobetalipoproteinemia pedigree
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Two distinct truncated apolipoprotein B species in a kindred with hypobetalipoproteinemia. / Krul, E. S.; Kinoshita, M.; Talmud, P.; Humphries, S. E.; Turner, Stephen T; Goldberg, A. C.; Cook, K.; Boerwinkle, E.; Schonfeld, G.
In: Arteriosclerosis, Vol. 9, No. 6, 1989, p. 856-868.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Two distinct truncated apolipoprotein B species in a kindred with hypobetalipoproteinemia
AU - Krul, E. S.
AU - Kinoshita, M.
AU - Talmud, P.
AU - Humphries, S. E.
AU - Turner, Stephen T
AU - Goldberg, A. C.
AU - Cook, K.
AU - Boerwinkle, E.
AU - Schonfeld, G.
PY - 1989
Y1 - 1989
N2 - Two novel, distinct truncated forms of apolipoprotein B (apo B) designated as apo B-90 and apo B-40 were found in five members of a kindred with hypobetalipoproteinemia. Sodium dodecyl sulfate gels and immunoblots of plasma or low density lipoprotein (LDL) (d = 1.019 to 1.063 g/ml) of the affected members demonstrated the presence of one or both of the truncated apo B bands. Employing four monoclonal anti-LDL antibodies with defined regional specificities, we demonstrated that amino terminal epitopes of the truncated apo Bs were intact, but that 10% and 60%, respectively, of the carboxyl terminal regions were absent. Thrombin digestion of apo B-90 generated an abnormally small T2 fragment, confirming that approximately 550 amino acids had been deleted from the carboxyl terminus of apo B-100. Restriction fragment length polymorphism analysis and variable number of tandem repeat typing of the 3' flanking hypervariable region of the apo B gene made it possible to distinguish all four parenteral alleles and therefore to follow the inheritance of the apo B variants through the family. This pedigree analysis confirmed the inheritance of the apo B-90 and apo B-40 identified by monoclonal antibody binding studies. Siblings heterozygous for apo B-90 or apo B-40 exhibited > 65% lower concentrations of apo B-90 or apo B-40 relative to apo B-100 and had 5th percentile LDL cholesterol concentrations. Compound heterozygotes (apo B-90/apo B-40) had the lowest LDL levels, and their LDL particles were small in size. The LDL of compound heterozygotes interacted with LDL receptors of cultured fibroblasts with greater than normal affinity, suggesting that the low level of apo B-90 in plasma may have been due to rapid clearance. The reasons for the low levels of apo B-40 are not known.
AB - Two novel, distinct truncated forms of apolipoprotein B (apo B) designated as apo B-90 and apo B-40 were found in five members of a kindred with hypobetalipoproteinemia. Sodium dodecyl sulfate gels and immunoblots of plasma or low density lipoprotein (LDL) (d = 1.019 to 1.063 g/ml) of the affected members demonstrated the presence of one or both of the truncated apo B bands. Employing four monoclonal anti-LDL antibodies with defined regional specificities, we demonstrated that amino terminal epitopes of the truncated apo Bs were intact, but that 10% and 60%, respectively, of the carboxyl terminal regions were absent. Thrombin digestion of apo B-90 generated an abnormally small T2 fragment, confirming that approximately 550 amino acids had been deleted from the carboxyl terminus of apo B-100. Restriction fragment length polymorphism analysis and variable number of tandem repeat typing of the 3' flanking hypervariable region of the apo B gene made it possible to distinguish all four parenteral alleles and therefore to follow the inheritance of the apo B variants through the family. This pedigree analysis confirmed the inheritance of the apo B-90 and apo B-40 identified by monoclonal antibody binding studies. Siblings heterozygous for apo B-90 or apo B-40 exhibited > 65% lower concentrations of apo B-90 or apo B-40 relative to apo B-100 and had 5th percentile LDL cholesterol concentrations. Compound heterozygotes (apo B-90/apo B-40) had the lowest LDL levels, and their LDL particles were small in size. The LDL of compound heterozygotes interacted with LDL receptors of cultured fibroblasts with greater than normal affinity, suggesting that the low level of apo B-90 in plasma may have been due to rapid clearance. The reasons for the low levels of apo B-40 are not known.
KW - apoprotein B
KW - hypobetalipoproteinemia pedigree
UR - http://www.scopus.com/inward/record.url?scp=0024353035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024353035&partnerID=8YFLogxK
M3 - Article
C2 - 2574033
AN - SCOPUS:0024353035
VL - 9
SP - 856
EP - 868
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 6
ER -