Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking
Abstract Background Glycerol-3-phosphate dehydrogenase 1 (GPD1) gene defect can cause hypertriglyceridemia (HTG), which usually occurs in infants. The gene defect has rarely been reported in adult HTG patients. In the present study, we described the clinical and functional analyses of a novel GPD1 m...
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2025-01-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-025-02088-6 |
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| author | Xiao-Yao Li Bei-Yuan Zhang Xin-Ran Liang Yan-Yu Han Min-Hua Cheng Mei Wei Ke Cao Xian-Cheng Chen Ming Chen Jian-Feng Duan Wen-Kui Yu |
| author_facet | Xiao-Yao Li Bei-Yuan Zhang Xin-Ran Liang Yan-Yu Han Min-Hua Cheng Mei Wei Ke Cao Xian-Cheng Chen Ming Chen Jian-Feng Duan Wen-Kui Yu |
| author_sort | Xiao-Yao Li |
| collection | DOAJ |
| description | Abstract Background Glycerol-3-phosphate dehydrogenase 1 (GPD1) gene defect can cause hypertriglyceridemia (HTG), which usually occurs in infants. The gene defect has rarely been reported in adult HTG patients. In the present study, we described the clinical and functional analyses of a novel GPD1 missense variant in a Chinese adult patient with recurrent hypertriglyceridemia‑related acute pancreatitis (HTG-AP), consuming a high-fat diet and smoking heavily. Methods Exome sequencing was used to analyze the DNA of the adult patient’s blood sample. It was found that there was a new variant of GPD1 gene-p.K327N, which was verified by gold standard-sanger sequencing method. In vitro, the corresponding plasmid was constructed and transfected into human renal HEK-293T cells, and GPD1 protein levels were detected. A biogenic analysis was performed to study the population frequency, conservation, and electric potential diagram of the new variant p.K327N. Finally, the previously reported GPD1 variants were sorted and their phenotypic relationships were compared. Results A novel heterozygous variant of GPD1, p.K327N (c.981G > C), was found in the proband. Furthermore, the patient’s daughter carried this variant, whereas his wife did not carry the variant. The proband with obesity suffered eight episodes of HTG-AP from the age of 36 years, and each onset of AP was correlated to high-fat diet consumption and heavy smoking. In vitro, this variant exerted a relatively mild effect on GPD1 functions, which were associated with its effect upon secretion (~ 25% of secretion decreased compared with that of the wild-type); thus, eventually impairing protein synthesis. Additionally, 36 patients with GPD1 variants found in previous studies showed significant transient HTG in infancy. The proband carrying the GDP1 variant was the first reported adult with recurrent HTG-AP. Conclusion We identified a novel GPD1 variant, p.K327N, in a Chinese adult male patient with recurrent HTG-AP. The variant probably exerted a mild effect on GPD1 functions. The heterozygosity of this GPD1 variant, in addition to high-fat diet consumption and heavy smoking, probably triggered HTG-AP in the patient. |
| format | Article |
| id | doaj-art-c48d0c25282c417fb028903c66b84834 |
| institution | Kabale University |
| issn | 1755-8794 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Medical Genomics |
| spelling | doaj-art-c48d0c25282c417fb028903c66b848342025-01-26T12:56:52ZengBMCBMC Medical Genomics1755-87942025-01-0118111410.1186/s12920-025-02088-6Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smokingXiao-Yao Li0Bei-Yuan Zhang1Xin-Ran Liang2Yan-Yu Han3Min-Hua Cheng4Mei Wei5Ke Cao6Xian-Cheng Chen7Ming Chen8Jian-Feng Duan9Wen-Kui Yu10Department of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese MedicineDepartment of Critical Care Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese MedicineDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Critical Care Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityAbstract Background Glycerol-3-phosphate dehydrogenase 1 (GPD1) gene defect can cause hypertriglyceridemia (HTG), which usually occurs in infants. The gene defect has rarely been reported in adult HTG patients. In the present study, we described the clinical and functional analyses of a novel GPD1 missense variant in a Chinese adult patient with recurrent hypertriglyceridemia‑related acute pancreatitis (HTG-AP), consuming a high-fat diet and smoking heavily. Methods Exome sequencing was used to analyze the DNA of the adult patient’s blood sample. It was found that there was a new variant of GPD1 gene-p.K327N, which was verified by gold standard-sanger sequencing method. In vitro, the corresponding plasmid was constructed and transfected into human renal HEK-293T cells, and GPD1 protein levels were detected. A biogenic analysis was performed to study the population frequency, conservation, and electric potential diagram of the new variant p.K327N. Finally, the previously reported GPD1 variants were sorted and their phenotypic relationships were compared. Results A novel heterozygous variant of GPD1, p.K327N (c.981G > C), was found in the proband. Furthermore, the patient’s daughter carried this variant, whereas his wife did not carry the variant. The proband with obesity suffered eight episodes of HTG-AP from the age of 36 years, and each onset of AP was correlated to high-fat diet consumption and heavy smoking. In vitro, this variant exerted a relatively mild effect on GPD1 functions, which were associated with its effect upon secretion (~ 25% of secretion decreased compared with that of the wild-type); thus, eventually impairing protein synthesis. Additionally, 36 patients with GPD1 variants found in previous studies showed significant transient HTG in infancy. The proband carrying the GDP1 variant was the first reported adult with recurrent HTG-AP. Conclusion We identified a novel GPD1 variant, p.K327N, in a Chinese adult male patient with recurrent HTG-AP. The variant probably exerted a mild effect on GPD1 functions. The heterozygosity of this GPD1 variant, in addition to high-fat diet consumption and heavy smoking, probably triggered HTG-AP in the patient.https://doi.org/10.1186/s12920-025-02088-6Glycerol-3-phosphate dehydrogenase 1Gene-environment interactionHypertriglyceridemiaMissense variantHypertriglyceridemia-induced acute pancreatitis |
| spellingShingle | Xiao-Yao Li Bei-Yuan Zhang Xin-Ran Liang Yan-Yu Han Min-Hua Cheng Mei Wei Ke Cao Xian-Cheng Chen Ming Chen Jian-Feng Duan Wen-Kui Yu Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking BMC Medical Genomics Glycerol-3-phosphate dehydrogenase 1 Gene-environment interaction Hypertriglyceridemia Missense variant Hypertriglyceridemia-induced acute pancreatitis |
| title | Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking |
| title_full | Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking |
| title_fullStr | Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking |
| title_full_unstemmed | Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking |
| title_short | Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking |
| title_sort | identification of a novel heterozygous gpd1 missense variant in a chinese adult patient with recurrent htg ap consuming a high fat diet and heavy smoking |
| topic | Glycerol-3-phosphate dehydrogenase 1 Gene-environment interaction Hypertriglyceridemia Missense variant Hypertriglyceridemia-induced acute pancreatitis |
| url | https://doi.org/10.1186/s12920-025-02088-6 |
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