Diminished gene expression of ileal apical sodium bile acid transporter explains impaired absorption of bile acid in patients with hypertriglyceridemia

Patients with type IV hyperlipoproteinemia, particularly those with familia l hypertriglyceridemia (FHT), hare impaired absorption elf bile acid, a def ect that may contribute to the hypertriglyceridemia (J. Lipid Res. 1995. 36 : 96-107). To determine whether this absorption defect is a result of abnor mal expression of the ileal apical sodium bile acid transporter (ASBT) gene , we biopsied the terminal ileum at colonoscopy in 28 subjects, 13 with hyp ertriglyceridemia and 15 control subjects, Of the 13 hypertriglyceridemic s ubjects, 10 had lipid profiles compatible with FHT (elevated very low densi ty lipoprotein [VLDL] triglycerides with normal LDL cholesterol). ASBT mRNA . levels were measured in these biopsies by RNase protection assay, using g lyceraldehyde dehydrogenase mRNA as a reference, ASBT protein was quantitat ed by Western blotting with an antibody to the carboxy-terminal 20 amino ac ids of the protein. The mean +/- SEM ASBT mRNA level in the control group w as 205.7 +/- 19.9 (arbitrary units) compared with 138.7 +/- 19.1 for all 13 hypertriglyceridemics (P = 0.03) and 141.7 +/- 20.8 in the 10 FHT patients (P = 0.05). Commensurate with these mRNA levels, the mean ASBT protein lev el in the control group was 126.2 +/- 22.6 versus 58.8 +/- 13.8 in hypertri glyceridemics (P = 0.02) and 61.8 +/- 15.2 in the FHT patients (P = 0.05). We conclude that impaired absorption of bile acid in type IV hypertriglycer idemia results from diminished expression of the ASBT gene in terminal ileu m.-Duane, W. C., L. A. Hartich, A. E. Bartman, and S. B. Ho. Diminished gen e expression of ileal apical sodium bile acid transporter explains impaired absorption of bile acid in patients with hypertriglyceridemia.