A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity
Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially HDLs. Association of the polymorphisms in the promoter region of the LIPC gene to post-heparin plasma HL activity and the plasma HDL-C concentration has been investigated thoroughly, but to date l...
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| Format: | Article |
| Language: | English |
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Elsevier
2002-10-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520327784 |
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| author | Zhiguang Su Sizhong Zhang Daniel W. Nebert Li Zhang Dejia Huang Yiping Hou Linchuan Liao Cuiying Xiao |
| author_facet | Zhiguang Su Sizhong Zhang Daniel W. Nebert Li Zhang Dejia Huang Yiping Hou Linchuan Liao Cuiying Xiao |
| author_sort | Zhiguang Su |
| collection | DOAJ |
| description | Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially HDLs. Association of the polymorphisms in the promoter region of the LIPC gene to post-heparin plasma HL activity and the plasma HDL-C concentration has been investigated thoroughly, but to date little is known about this in the Chinese. In the present study, we analyzed the polymorphisms in the promoter region of LIPC gene in Chinese patients with coronary artery disease (CAD) using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. As the result, a novel single nucleotide polymorphism −586T-to-C was identified and no linkage of this variant with other polymorphisms in the promoter was found. Compared with the nonsymptomatic control subjects, excess of carriers of the −586T/C substitution were detected in the CAD patients (43% vs. 31%, χ2 = 4.597, degree of freedom = 2, P = 0.032).The –586C allele carriers in the CAD patients had a significantly higher HDL-C level than the noncarriers (1.13 ± 0.24 mmol/l vs. 0.91 ± 0.14 mmol/l, P < 0.05). To test the functionality of this substitution, luciferase-reporter assays was performed in HepG2 cells. Promoter activity of the −586C construct was decreased 2-fold than the −586T construct.Our studies suggest that a T-to-C substitution at −586 of the LIPC promoter is associated with a lowered HL activity and that this variation may contribute to the increased plasma HDL-C concentration in the Chinese. |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T19:41:15Z |
| publishDate | 2002-10-01 |
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| series | Journal of Lipid Research |
| spelling | doaj.art-39a6864820824a19a919c3fc53ba10f02022-12-21T20:08:14ZengElsevierJournal of Lipid Research0022-22752002-10-01431015951601A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activityZhiguang Su0Sizhong Zhang1Daniel W. Nebert2Li Zhang3Dejia Huang4Yiping Hou5Linchuan Liao6Cuiying Xiao7Department of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaDepartment of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaDepartment of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaDepartment of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaDepartment of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaDepartment of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaDepartment of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaDepartment of Medical Genetics, West China Hospital, Sichuan University, China; Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China; Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH; Department of Cardiology, West China Hospital, Sichuan University, ChinaHepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially HDLs. Association of the polymorphisms in the promoter region of the LIPC gene to post-heparin plasma HL activity and the plasma HDL-C concentration has been investigated thoroughly, but to date little is known about this in the Chinese. In the present study, we analyzed the polymorphisms in the promoter region of LIPC gene in Chinese patients with coronary artery disease (CAD) using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. As the result, a novel single nucleotide polymorphism −586T-to-C was identified and no linkage of this variant with other polymorphisms in the promoter was found. Compared with the nonsymptomatic control subjects, excess of carriers of the −586T/C substitution were detected in the CAD patients (43% vs. 31%, χ2 = 4.597, degree of freedom = 2, P = 0.032).The –586C allele carriers in the CAD patients had a significantly higher HDL-C level than the noncarriers (1.13 ± 0.24 mmol/l vs. 0.91 ± 0.14 mmol/l, P < 0.05). To test the functionality of this substitution, luciferase-reporter assays was performed in HepG2 cells. Promoter activity of the −586C construct was decreased 2-fold than the −586T construct.Our studies suggest that a T-to-C substitution at −586 of the LIPC promoter is associated with a lowered HL activity and that this variation may contribute to the increased plasma HDL-C concentration in the Chinese.http://www.sciencedirect.com/science/article/pii/S0022227520327784LIPC promotersingle nucleotide polymorphismcoronary artery diseasetransient transfection |
| spellingShingle | Zhiguang Su Sizhong Zhang Daniel W. Nebert Li Zhang Dejia Huang Yiping Hou Linchuan Liao Cuiying Xiao A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity Journal of Lipid Research LIPC promoter single nucleotide polymorphism coronary artery disease transient transfection |
| title | A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity |
| title_full | A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity |
| title_fullStr | A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity |
| title_full_unstemmed | A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity |
| title_short | A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity |
| title_sort | novel allele in the promoter of the hepatic lipase is associated with increased concentration of hdl c and decreased promoter activity |
| topic | LIPC promoter single nucleotide polymorphism coronary artery disease transient transfection |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520327784 |
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