دورية أكاديمية
Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis
| العنوان: | Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis |
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| المؤلفون: | Li, Xiao-Yao, Pu, Na, Chen, Wei-Wei, Shi, Xiao-Lei, Zhang, Guo-Fu, Ke, Lu, Ye, Bo, Tong, Zhi-Hui, Wang, Yu-Hui, Liu, George, Chen, Jian-Min, Yang, Qi, Li, Wei-Qin, Li, Jie-Shou |
| المساهمون: | Nanjing University (NJU), Yangzhou University, Peking University Beijing, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO) |
| المصدر: | ISSN: 1476-511X ; Lipids in Health and Disease ; https://hal.science/hal-03700919Test ; Lipids in Health and Disease, 2020, 19 (1), pp.63. ⟨10.1186/s12944-020-01249-z⟩. |
| بيانات النشر: | HAL CCSD BioMed Central |
| سنة النشر: | 2020 |
| المجموعة: | Université de Bretagne Occidentale: HAL |
| مصطلحات موضوعية: | Gene-environment interaction, Genotype and phenotype relationship, Hypertriglyceridemia-induced acute pancreatitis, LPL gene, Lipoprotein lipase, Nonsense variant, Triglyceride, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Abstract Background Hypertriglyceridemia (HTG) is a leading cause of acute pancreatitis. HTG can be caused by either primary (genetic) or secondary etiological factors, and there is increasing appreciation of the interplay between the two kinds of factors in causing severe HTG. Objectives The main aim of this study was to identify the genetic basis of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) in a Chinese family with three affected members (the proband, his mother and older sister). Methods The entire coding and flanking sequences of LPL , APOC2 , APOA5 , GPIHBP1 and LMF1 genes were analyzed by Sanger sequencing. The newly identified LPL nonsense variant was subjected to functional analysis by means of transfection into HEK-293 T cells followed by Western blot and activity assays. Previously reported pathogenic LPL nonsense variants were collated and compared with respect to genotype and phenotype relationship. Results We identified a novel nonsense variant, p.Gln118* (c.351C > T), in the LPL gene, which co-segregated with HTG-AP in the Chinese family. We provided in vitro evidence that this variant resulted in a complete functional loss of the affected LPL allele. We highlighted a role of alcohol abuse in modifying the clinical expression of the disease in the proband. Additionally, our survey of 12 previously reported pathogenic LPL nonsense variants (in 20 carriers) revealed that neither serum triglyceride levels nor occurrence of HTG-AP was distinguishable among the three carrier groups, namely, simple homozygotes, compound heterozygotes and simple heterozygotes. Conclusions Our findings, taken together, generated new insights into the complex etiology and expression of HTG-AP. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32264896; hal-03700919; https://hal.science/hal-03700919Test; PUBMED: 32264896; PUBMEDCENTRAL: PMC7140582 |
| DOI: | 10.1186/s12944-020-01249-z |
| الإتاحة: | https://doi.org/10.1186/s12944-020-01249-zTest https://hal.science/hal-03700919Test |
| رقم الانضمام: | edsbas.274C8705 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12944-020-01249-z |
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