Exonic variants of GPIHBP1 gene in Thai subjects with severe hypertriglyceridemia
Keywords:
GPIHBP1, genetics, hypertriglyceridemia, triglyceride, variantsAbstract
Background: Hypertriglyceridemia (HTG) is one of the risk factors for cardiovascular disease and acute pancreatitis. It is associated with genetic variations in various genes involved in triglyceride metabolism. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) encodes a membrane protein involved in an intravascular triglyceride hydrolysis.
Objective: The purpose of this study was to examine the genetic variants in the exons of GPIHBP1 gene in Thai subjects with severe HTG.
Methods: All 4 exons of the GPIHBP1 gene were sequenced in 101 Thai subjects with severe HTG. All subjects had triglyceride levels e” 10 mmol/L or 886 mg/dL. Subjects with normolipidemia (n = 111) were used as controls.
Results: The allele frequency of the common p.Cys14Phe variant (rs11538389) in control group was higher than in severe HTG group (0.523 vs. 0.386, P = 0.11). Interestingly, 2 rare missense variants were identified in 3 HTG patients. A homozygous p.Ser107Cys (rs587777643) was found in 1 patient and a heterozygous p.Arg16Gln (rs748509621) was found in 2 patients. These two rare variants were not observed in the normolipidemic controls.
Conclusion: Our study demonstrated that p.Ser107Cys and p.Arg16Gln variants were exclusively found in HTG patients. The finding suggested that these 2 variations in GPIHBP1 gene might be a rare genetic cause of severe HTG among Thai population.
Downloads
References
Simons-Linares CR, Jang S, Sanaka M, Bhatt A, LopezR, Vargo J, et al. The triad of diabetes ketoacidosis,hypertriglyceridemia and acute pancreatitis. How doesit affect mortality and morbidity?: A 10-year analysisof the National Inpatient Sample. Medicine (Baltimore)2019;98:e14378. https://doi.org/10.1097/MD.0000000000014378 PMid:30762737 PMCid:PMC6408121
Zhang R, Deng L, Jin T, Zhu P, Shi N, Jiang K, et al.Hypertriglyceridaemia-associated acute pancreatitis:diagnosis and impact on severity. HPB (Oxford)2019;21:1240-9. https://doi.org/10.1016/j.hpb.2019.01.015 PMid:30885545
Falko JM. Familial Chylomicronemia Syndrome: AClinical Guide For Endocrinologists. Endocr Pract2018;24:756-63. https://doi.org/10.4158/EP-2018-0157 PMid:30183397
Paquette M, Bernard S, Hegele RA, Baass A.Chylomicronemia: Differences between familialchylomicronemia syndrome and multifactorialchylomicronemia. Atherosclerosis 2019;283:137-42. https://doi.org/10.1016/j.atherosclerosis.2018.12.019 PMid:30655019
Shah NP, Cho L, Ahmed HM. Familial ChylomicronemiaSyndrome: Clinical Characteristics and Long-TermCardiovascular Outcomes. J Am Coll Cardiol2018;72:1177-9.
Plengpanich W, Muanpetch S, Charoen S,Kiateprungvej A, Khovidhunkit W. Genetic andfunctional studies of the LMF1 gene in Thai patientswith severe hypertriglyceridemia. Mol Genet MetabRep 2020;23:100576. https://doi.org/10.1016/j.ymgmr.2020.100576 PMid:32190547 PMCid:PMC7068683
Jin JL, Sun D, Cao YX, Zhang HW, Guo YL, Wu NQ,et al. Intensive genetic analysis for Chinese patientswith very high triglyceride levels: Relations ofmutations to triglyceride levels and acute pancreatitis.EBioMedicine 2018;38:171-7. https://doi.org/10.1016/j.ebiom.2018.11.001 PMid:30420299 PMCid:PMC6306308
Lee CJ, Oum CY, Lee Y, Park S, Kang SM, Choi D, et al.Variants of Lipolysis-Related Genes in Korean Patientswith Very High Triglycerides. Yonsei Med J 2018;59:148-53. https://doi.org/10.3349/ymj.2018.59.1.148 PMid:29214790 PMCid:PMC5725353
Matsunaga A, Nagashima M, Yamagishi H, Saku K.Variants of Lipid-Related Genes in Adult JapanesePatients with Severe Hypertriglyceridemia. JAtheroscler Thromb 2020;27:1264-77. https://doi.org/10.5551/jat.51540 PMid:32115487 PMCid:PMC7840158
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Chulalongkorn Medical Journal
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
