Nature Genetics
36, 371 - 376 (2004)
Published online: 29 February 2004; | doi:10.1038/ng1320
Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1)Päivi Pajukanta1, Heidi E Lilja2, Janet S Sinsheimer1, 3, Rita M Cantor1, 4, Aldons J Lusis1, 5, 6, 7, Massimiliano Gentile2, Xiaoqun Joyce Duan8, Aino Soro-Paavonen9, Jussi Naukkarinen2, Janna Saarela2, Markku Laakso10, Christian Ehnholm2, Marja-Riitta Taskinen9
& Leena Peltonen1, 21
Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095−7088, USA. 2
Department of Molecular Medicine, National Public Health Institute, Finland and Department of Medical Genetics, University of Helsinki, Biomedicum, 00290 Helsinki, Finland. 3
Departments of Biomathematics and Biostatistics, David Geffen School of Medicine at UCLA; University of California, Los Angeles, California 90095−7088, USA. 4
Department of Pediatrics, David Geffen School of Medicine at UCLA; University of California, Los Angeles, California 90095−7088, USA. 5
Departments of Microbiology and Molecular Genetics, David Geffen School of Medicine at UCLA; University of California, Los Angeles, California 90095−7088, USA. 6
Department of Medicine, David Geffen School of Medicine at UCLA; University of California, Los Angeles, California 90095−7088, USA. 7
Molecular Biology Institute;, David Geffen School of Medicine at UCLA; University of California, Los Angeles, California 90095−7088, USA. 8
UCLA-DOE Institute for Genomics and Proteomics, David Geffen School of Medicine at UCLA; University of California, Los Angeles, California 90095−7088, USA. 9
Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. 10
University of Kuopio, Kuopio, Finland.
Correspondence should be addressed to Päivi Pajukanta ppajukanta@mednet.ucla.edu or Leena Peltonen leena.peltonen@ktl.fiFamilial combined hyperlipidemia (FCHL), characterized by elevated levels of serum total cholesterol, triglycerides or both1,
2, is observed in about 20% of individuals with premature coronary heart disease1. We previously identified a locus linked to FCHL on 1q21−q23 in Finnish families with the disease3. This region has also been linked to FCHL in families from other populations4,
5,
6 as well as to type 2 diabetes mellitus7,
8,
9,
10,
11,
12. These clinical entities have several overlapping phenotypic features, raising the possibility that the same gene may underlie the obtained linkage results. Here, we show that the human gene encoding thioredoxin interacting protein (TXNIP) on 1q, which underlies combined hyperlipidemia in mice13, is not associated with FCHL. We show that FCHL is linked and associated with the gene encoding upstream transcription factor 1 (USF1) in 60 extended families with FCHL, including 721 genotyped individuals (P = 0.00002), especially in males with high triglycerides (P = 0.0000009). Expression profiles in fat biopsy samples from individuals with FCHL seemed to differ depending on their carrier status for the associated USF1 haplotype. USF1 encodes a transcription factor known to regulate several genes of glucose and lipid metabolism14,
15,
16,
17.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated. NEWS AND VIEWSUSF1 on trialNature Genetics News and Views (01 Apr 2004)
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