Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in context
Background: Severe hypertriglyceridemia (SHTG, TG ≥5·65 mmol/L), a disease, usually resulting from a combination of genetic and environmental factors, may increase the risk of acute pancreatitis (AP). However, previous genetic analysis has been limited by lacking of related observation of gene to AP...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-12-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418304948 |
| _version_ | 1818475213001588736 |
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| author | Jing-Lu Jin Di Sun Ye-Xuan Cao Hui-Wen Zhang Yuan-Lin Guo Na-Qiong Wu Cheng-Gang Zhu Ying Gao Qiu-Ting Dong Geng Liu Qian Dong Jian-Jun Li |
| author_facet | Jing-Lu Jin Di Sun Ye-Xuan Cao Hui-Wen Zhang Yuan-Lin Guo Na-Qiong Wu Cheng-Gang Zhu Ying Gao Qiu-Ting Dong Geng Liu Qian Dong Jian-Jun Li |
| author_sort | Jing-Lu Jin |
| collection | DOAJ |
| description | Background: Severe hypertriglyceridemia (SHTG, TG ≥5·65 mmol/L), a disease, usually resulting from a combination of genetic and environmental factors, may increase the risk of acute pancreatitis (AP). However, previous genetic analysis has been limited by lacking of related observation of gene to AP. Methods: The expanding genetic sequencing including 15 TG-related genes (LPL, LMF1, APOC2, GPIHBP1, GCKR, ANGPTL3, APOB, APOA1-A4-C3-A5, TRIB1, CETP, APOE, and LIPI) was performed within 103 patients who were diagnosed with primary SHTG and 46 age- and sex-matched normal controls. Findings: Rare variants were found in 46 patients and 12 controls. The detection rate of rare variants in SHTG group increased by 19·5% via intensive genetic analysis. Presence of rare variants in LPL, APOA5, five LPL molecular regulating genes and all the sequenced genes were found to be associated with SHTG (p < 0·05). Of noted, patients with history of AP presented higher frequency of rare variants in LPL gene and all the LPL molecular regulating genes (27·8% vs.4·7% and 50·0% vs. 20·0%). The risk scores for SHTG determined by common TG-associated variants were increased in subgroups according to the extent of SHTG when they were compared with that of controls. Finally, patients without rare variants within SHTG group also presented higher risk scores than control group (p < 0·05). Interpretation: Expanding genetic analysis had a higher detection rate of rare variants in patients with SHTG. Rare variants in LPL and its molecular regulating genes could increase the risk of AP among Chinese patients with SHTG. Fund: This work was partially supported by the Capital Health Development Fund (201614035) and CAMS. Major Collaborative Innovation Project (2016-I2M-1-011) awarded to Dr. Jian-Jun Li, MD, PhD. Keywords: Hypertriglyceridemia, Genetic analysis, Acute pancreatitis |
| first_indexed | 2024-12-10T09:10:06Z |
| format | Article |
| id | doaj.art-d1dfc55575b24fc69c77f9a9d021a3d3 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-10T09:10:06Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-d1dfc55575b24fc69c77f9a9d021a3d32022-12-22T01:55:02ZengElsevierEBioMedicine2352-39642018-12-0138171177Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in contextJing-Lu Jin0Di Sun1Ye-Xuan Cao2Hui-Wen Zhang3Yuan-Lin Guo4Na-Qiong Wu5Cheng-Gang Zhu6Ying Gao7Qiu-Ting Dong8Geng Liu9Qian Dong10Jian-Jun Li11Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaDivision of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaCorresponding author.; Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, ChinaBackground: Severe hypertriglyceridemia (SHTG, TG ≥5·65 mmol/L), a disease, usually resulting from a combination of genetic and environmental factors, may increase the risk of acute pancreatitis (AP). However, previous genetic analysis has been limited by lacking of related observation of gene to AP. Methods: The expanding genetic sequencing including 15 TG-related genes (LPL, LMF1, APOC2, GPIHBP1, GCKR, ANGPTL3, APOB, APOA1-A4-C3-A5, TRIB1, CETP, APOE, and LIPI) was performed within 103 patients who were diagnosed with primary SHTG and 46 age- and sex-matched normal controls. Findings: Rare variants were found in 46 patients and 12 controls. The detection rate of rare variants in SHTG group increased by 19·5% via intensive genetic analysis. Presence of rare variants in LPL, APOA5, five LPL molecular regulating genes and all the sequenced genes were found to be associated with SHTG (p < 0·05). Of noted, patients with history of AP presented higher frequency of rare variants in LPL gene and all the LPL molecular regulating genes (27·8% vs.4·7% and 50·0% vs. 20·0%). The risk scores for SHTG determined by common TG-associated variants were increased in subgroups according to the extent of SHTG when they were compared with that of controls. Finally, patients without rare variants within SHTG group also presented higher risk scores than control group (p < 0·05). Interpretation: Expanding genetic analysis had a higher detection rate of rare variants in patients with SHTG. Rare variants in LPL and its molecular regulating genes could increase the risk of AP among Chinese patients with SHTG. Fund: This work was partially supported by the Capital Health Development Fund (201614035) and CAMS. Major Collaborative Innovation Project (2016-I2M-1-011) awarded to Dr. Jian-Jun Li, MD, PhD. Keywords: Hypertriglyceridemia, Genetic analysis, Acute pancreatitishttp://www.sciencedirect.com/science/article/pii/S2352396418304948 |
| spellingShingle | Jing-Lu Jin Di Sun Ye-Xuan Cao Hui-Wen Zhang Yuan-Lin Guo Na-Qiong Wu Cheng-Gang Zhu Ying Gao Qiu-Ting Dong Geng Liu Qian Dong Jian-Jun Li Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in context EBioMedicine |
| title | Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in context |
| title_full | Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in context |
| title_fullStr | Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in context |
| title_full_unstemmed | Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in context |
| title_short | Intensive genetic analysis for Chinese patients with very high triglyceride levels: Relations of mutations to triglyceride levels and acute pancreatitisResearch in context |
| title_sort | intensive genetic analysis for chinese patients with very high triglyceride levels relations of mutations to triglyceride levels and acute pancreatitisresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418304948 |
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