segregation of lipg, cetp, and galnt2 mutations in caucasian families with extremely high hdl cholesterol种族隔离的lipg,cetp和galnt2突变与极高的高密度脂蛋白胆固醇在白人家庭.pdfVIP

Segregation of LIPG, CETP, and GALNT2 Mutations in Caucasian Families with Extremely High HDL Cholesterol 1. 2. 1,3 1 4 Ian Tietjen , G. Kees Hovingh , Roshni R. Singaraja , Chris Radomski , Amina Barhdadi , 1 1 1 1 1 Jason McEwen , Elden Chan , Maryanne Mattice , Annick Legendre , Patrick L. Franchini , ´4 2 3 Marie-Pierre Dube , John J. P. Kastelein , Michael R. Hayden * 1 Xenon Pharmaceuticals Inc., Burnaby, Canada, 2 Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands, 3 Centre for ´ Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada, 4 Montreal Heart Institute, Montreal, Canada Abstract To date, few mutations are described to underlie highly-elevated HDLc levels in families. Here we sequenced the coding regions and adjacent sequence of the LIPG, CETP, and GALNT2 genes in 171 unrelated Dutch Caucasian probands with HDLc$90th percentile and analyzed segregation of mutations with lipid phenotypes in family members. In these probands, mutations were most frequent in LIPG (12.9%) followed by GALNT2 (2.3%) and CETP (0.6%). A total of 6 of 10 mutations in these three genes were novel (60.0%), and mutations segregated with elevated HDLc in families. Interestingly, the LIPG mutations N396S and R476W, which usually result in elevated HDLc, were unexpectedly found in 6 probands with low HD