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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:2039.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Analysis of the Ileal Bile Acid Transporter Gene, SLC10A2, in Subjects With Familial Hypertriglyceridemia

Martha W. Love; Ann L. Craddock; Bo Angelin; John D. Brunzell; William C. Duane; Paul A. Dawson

From the Department of Internal Medicine (M.W.L., A.L.C., P.A.D.), Wake Forest University School of Medicine, Winston-Salem, NC; the Center for Metabolism and Endocrinology (B.A.), Department of Medicine, and Molecular Nutrition Unit (B.A.), Center for Nutrition and Toxicology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden; the Division of Metabolism, Endocrinology, and Nutrition (J.D.B.), Department of Medicine, University of Washington, Seattle; and GI Section (W.C.D.), Department of Medicine, Veterans Affairs Medical Center, University of Minnesota, Minneapolis.

Correspondence to Dr Paul A. Dawson, Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157. E-mail pdawson{at}wfubmc.edu

Familial hypertriglyceridemia (FHTG), a disease characterized by elevated plasma very low density lipoprotein triglyceride levels, has been associated with impaired intestinal absorption of bile acids. The aim of this study was to test the hypothesis that defects in the active ileal absorption of bile acids are a primary cause of FHTG. Single-stranded conformation polymorphism analysis was used to screen the ileal Na⁺/bile acid cotransporter gene (SLC10A2) for FHTG-associated mutations. Analysis of 20 hypertriglyceridemic patients with abnormal bile acid metabolism revealed 3 missense mutations (V98I, V159I, and A171S), a frame-shift mutation (646insG) at codon 216, and 4 polymorphisms in the 5' flanking sequence of SLC10A2. The SLC10A2 missense mutations and 5' flanking sequence polymorphisms were not correlated with bile acid production or turnover in the hypertriglyceridemic patients and were equally prevalent in the unaffected control subjects. In transfected COS cells, the V98I, V159I, and A171S isoforms all transported bile acids similar to the wild-type SLC10A2. The 646insG frame-shift mutation abolished bile acid transport activity in transfected COS cells but was found in only a single FHTG patient. These findings indicate that the decreased intestinal bile acid absorption in FHTG patients is not commonly associated with inherited defects in SLC10A2.

Key Words: bile acids • hypertriglyceridemia • genetics • complex disease

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