| Glucuronic Acid Epimerase is Associated with Plasma Triglyceride and High-Density Lipoprotein Cholesterol Levels in Turks. | |
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MedLine Citation:
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PMID: 21488854 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We narrowed chromosome 15q21-23 linkage to plasma high-density lipoprotein cholesterol (HDL-C) levels in Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with HDL-C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, and rs3865014) were associated with triglyceride and HDL-C levels in males (nonpermuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached multiple-testing significance (p < 0.05) in both males and females (n= 2612). Similar results were obtained in the second cohort (n= 1164). Interestingly, at the GLCE locus, bounded by recombination hotspots, Turks had a minor allele frequency of SNPs resembling Chinese more than European ancestry; adjoining regions resembled the European pattern. Studies of glce(+/-) apoe(-/-) mice fed a chow or high-fat diet supported a role for GLCE in lipid metabolism. Thus, SNPs in GLCE are associated with triglyceride and HDL-C levels in Turks, and mouse studies support a role for glce in lipid metabolism. |
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Authors:
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Uğur Hodoğlugil; David W Williamson; Yi Yu; Lindsay A Farrer; Robert W Mahley |
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Publication Detail:
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Type: JOURNAL ARTICLE |
Journal Detail:
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Title: Annals of human genetics Volume: 75 ISSN: 1469-1809 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-4-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0416661 Medline TA: Ann Hum Genet Country: - |
Other Details:
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Languages: ENG Pagination: 398-417 Citation Subset: - |
Copyright Information:
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© 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London. |
Affiliation:
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Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA Gladstone Institute of Neurological Disease, San Francisco, CA, USA Departments of Medicine and Pathology, University of California, San Francisco, CA, USA Departments of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA, USA Departments of Neurology, and Genetics & Genomics, Boston University School of Medicine, Boston, MA, USA Departments of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, MA, USA. |
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