Prevalence of lipoprotein lipase mutation in patients with severe hypertriglyceridemia and the characteristic features of hypertriglyceridemic pancreatitis
Öz
Aim: We conducted a retrospective study with the aim of determining the prevalence of lipoprotein
lipase (LPL) mutation in patients with severe hypertriglyceridemia (HTG) and to study differences in
characteristic features of HTG induced acute pancreatitis (AP).
Materials and Methods: Seventy adults with a serum triglyceride (TG) level ≥500 mg/dL were
included in the study. Baseline characteristics, LPL mutation and risk factors between those with and
without HTG-AP were compared.
Results: The mean age was 43 ± 12 years, and males accounted for 55.7%. Of the patients 35 had
TG level <2000 mg/dL, and 35 patients had TG ≥2000 mg/dL. LPL mutation was found in 19 (27.1%)
of the cases. The prevalence of AP was 67.1% (47 patients). Younger age, TG level, hemoglobin A1c
(HbA1c) were significantly independent risk factors for the development of HTG-AP. When patients
were divided into groups based on TG levels (group 1 with TG <2000 mg/dL, group 2 TG ≥2000
mg/dL) the prevalence of AP was significantly higher in group 2 (51.4% vs. 82.9%). Age and HbA1c
lost their significance for development of AP. When the relationship between the frequency of AP and
TG value was evaluated, the specificity of TG threshold value for developing AP was found to be 2235
mg/dL. There was no difference in prevalence of AP and TG level between mutation detected and
undetected groups.
Conclusion: There was no difference in prevalence of AP and TG level between variant detected and
undetected groups. In contrast to the literature, higher levels of TG cut-off points to develop AP was
determined.
Anahtar Kelimeler
Kaynakça
- DeFrances CJ, Podgornik MN. 2004 National Hospital Discharge Survey. Adv Data 2006;(371):1-19. PMID: 16703980.
- Saharia P, Margolis S, Zuidema GD, Cameron JL. Acute pancreatitis with hyperlipemia: studies with an isolated perfused canine pancreas. Surgery 1977;82(1):60-7. PMID: 877857.
- Valdivielso P, Ramírez-Bueno A, Ewald N. Current knowledge of hypertriglyceridemic pancreatitis. Eur J Intern Med 2014;25(8):689-94. doi: 10.1016/j.ejim.2014.08.008.
- Havel RJ. Pathogenesis, differentiation and management of hyper-triglyceridemia. Adv Intern Med 1969;15:117-54. PMID: 4908616.
- Burnett JR, Hooper AJ, Hegele RA. Familial Lipoprotein Lipase Deficiency. 1999 Oct 12 [updated 2017 Jun 22]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
- Davidson MH, Toth PP, Maki KC. Familial lipoprotein lipase deficiency. Therapeutic Lipidology. Humana Press. Totowa, NJ. 2007:465-6.
- Demacker PNM, Stalenhoef AFH. Familial lipoprotein lipase deficiency. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:465-6.
- Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97(9):2969-89. doi: 10.1210/jc.2011-3213.
- Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285(19):2486-97. doi: 10.1001/jama.285.19.2486.
- Hegele RA. Monogenic dyslipidemias: window on determinants of plasma lipoprotein metabolism. Am J Hum Genet 2001;69(6):1161-77. doi: 10.1086/324647.
- Gaudet D, Methot J, Kastelein J. Gene therapy for lipoprotein lipase deficiency. Curr Opin Lipidol 2012;23(4):310-20. doi: 10.1097/MOL.0b013e3283555a7e.
- Tenner S, Baillie J, DeWitt J, Vege SS, American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108(9):1400-15; 1416. doi: 10.1038/ajg.2013.218.
- Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation 1999;99(22):2901-7. doi: 10.1161/01.cir.99.22.2901.
- Wright WT, Young IS, Nicholls DP, Graham CA. Genetic screening of the LPL gene in hypertriglyceridaemic patients. Atherosclerosis 2008;199(1):187-92. doi: 10.1016/j.atherosclerosis.2007.10.029.
- Monsalve MV, Henderson H, Roederer G, et al. A missense mutation at codon 188 of the human lipoprotein lipase geneis a frequent cause of lipoprotein lipase deficiency in persons ofdifferent ancestries. J Clin Invest 1990;86(3):728-34. doi: 10.1172/JCI114769.
- Hata A, Ridinger DN, Sutherland SD, et al. Missense mutations in exon 5 of the human lipoprotein lipase gene: inactivation correlates with loss of dimerization. J Biol Chem 1992;267(8):20132-9. PMID: 1400331. doi: 10.1016/S0021-9258(19)88676-3.
- Ooi EMM, Russell BS, Olson E, et al. Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations. Arterioscler Thromb Vasc Biol 2012;32(2):459-66. doi:10.1161/ATVBAHA.111.238493.
- Dron JS, Wang J, Cao H, et al. Severe hypertriglyceridemia is primarily polygenic. J Clin Lipidol 2019;13(1):80-8. doi: 10.1016/j.jacl.2018.10.006.
- Dron JS, Hegele RA. Polygenic influences on dyslipidemias. Curr Opin Lipidol 2018;29(2):133-43. doi: 10.1097/MOL.0000000000000482
- Carr RA, Rejowski BJ, Cote GA, Pitt HA, Zyromski NJ. Systematic review of hypertriglyceridemia-induced acute pancreatitis: a more virulent etiology? Pancreatology 2016;16(4):469-76. doi: 10.1016/j.pan.2016.02.011.
- Amblee A, Mohananey D, Morkos M, et al. Acute Pancreatitis in Patients with Severe Hypertriglyceridemia in a Multi-Ethnic Minority Population. Endocr Pract 2018;24(5):429-36. doi: 10.4158/EP-2017-0178.
- Sandhu S, Al-Sarraf A, Taraboanta C, Frohlich J, Francis GA. Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study. Lipids Health Dis 2011;10:157. doi: 10.1186/1476-511X-10-157.
- Schaap-Fogler M, Schurr D, Schaap T, Leitersdorf E, Rund D. Long-term plasma exchange for severe refractory hypertriglyceridemia: a decade of experience demonstrates safety and efficacy. J Clin Apher 2009;24(6):254-8. doi: 10.1002/jca.20224.
- Padmanabhan A, Connelly-Smith L, Aqui N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher 2019;34(3):171-354. doi: 10.1002/jca.21705.
- Zhang XL, Li F, Zhen YM, Li A, Fang Y. Clinical Study of 224 Patients with Hypertriglyceridemia Pancreatitis. Chin Med J (Engl) 2015;128(15):2045-9. doi: 10.4103/0366-6999.161361
Şiddetli hipertrigliseridemili hastalarda lipoprotein lipaz mutasyon prevalansı ve hipertrigliseridemik pankreatitin karakteristik özellikleri
Öz
Amaç: Şiddetli hipertrigliseridemili (HTG) hastalarda lipoprotein lipaz (LPL) mutasyon prevalansını
belirlemek ve LPL varyantı olan ve olmayan HTG kaynaklı akut pankreatitin (AP) karakteristik
özelliklerindeki farklılıkları araştırmak amacıyla retrospektif bir çalışma amaçladık.
Gereç ve Yöntem: Çalışmaya serum trigliserid (TG) düzeyi ≥500 mg/dL olan 70 yetişkin dahil edildi.
HTG-AP'i olan ve olmayan olgular arasındaki temel özellikler, LPL mutasyonunu ve risk faktörleri
karşılaştırıldı.
Bulgular: Ortalama yaş 43 ± 12 idi ve erkekler çalışma popülasyonunun %55.7'sini oluşturuyordu. 35
hastada TG düzeyi <2000 mg/dL, 35 hastada TG ≥2000 mg/dL idi. 19 olguda (%27.1) LPL mutasyonu
saptandı. AP prevalansı %67.1 (47 hasta) idi. Korelasyon analizinde genç yaş, TG düzeyi, hemoglobin
A1c (HbA1c) HTG-AP gelişimi için anlamlı derecede bağımsız risk faktörleriydi. Hastalar TG
düzeylerine göre iki gruba ayrıldığında (TG <2000 mg/dL olanlar grup 1, grup 2 TG ≥2000 mg/dL) AP
prevalansı grup 2'de anlamlı olarak daha yüksekti (%51.4'e karşı %82.9), yaş ile HbA1c AP gelişimi
için anlamsız saptandı. AP sıklığı ile TG değeri arasındaki ilişki değerlendirildiğinde, TG eşik değerinin
pankreatit gelişimi için özgüllüğü 2235 mg/dL bulunmuştur. Mutasyon saptanan ve saptanamayan
gruplar arasında AP ve TG prevalansı açısından fark saptanmamıştır.
Sonuç: Varyant saptanan ve saptanmayan gruplar arasında AP ve TG düzeyi açısından fark yoktu.
Literatürden farklı olarak, AP geliştirmek için daha yüksek seviyelerde TG kesme noktası belirlendi.
Anahtar Kelimeler
Kaynakça
- DeFrances CJ, Podgornik MN. 2004 National Hospital Discharge Survey. Adv Data 2006;(371):1-19. PMID: 16703980.
- Saharia P, Margolis S, Zuidema GD, Cameron JL. Acute pancreatitis with hyperlipemia: studies with an isolated perfused canine pancreas. Surgery 1977;82(1):60-7. PMID: 877857.
- Valdivielso P, Ramírez-Bueno A, Ewald N. Current knowledge of hypertriglyceridemic pancreatitis. Eur J Intern Med 2014;25(8):689-94. doi: 10.1016/j.ejim.2014.08.008.
- Havel RJ. Pathogenesis, differentiation and management of hyper-triglyceridemia. Adv Intern Med 1969;15:117-54. PMID: 4908616.
- Burnett JR, Hooper AJ, Hegele RA. Familial Lipoprotein Lipase Deficiency. 1999 Oct 12 [updated 2017 Jun 22]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
- Davidson MH, Toth PP, Maki KC. Familial lipoprotein lipase deficiency. Therapeutic Lipidology. Humana Press. Totowa, NJ. 2007:465-6.
- Demacker PNM, Stalenhoef AFH. Familial lipoprotein lipase deficiency. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:465-6.
- Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97(9):2969-89. doi: 10.1210/jc.2011-3213.
- Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285(19):2486-97. doi: 10.1001/jama.285.19.2486.
- Hegele RA. Monogenic dyslipidemias: window on determinants of plasma lipoprotein metabolism. Am J Hum Genet 2001;69(6):1161-77. doi: 10.1086/324647.
- Gaudet D, Methot J, Kastelein J. Gene therapy for lipoprotein lipase deficiency. Curr Opin Lipidol 2012;23(4):310-20. doi: 10.1097/MOL.0b013e3283555a7e.
- Tenner S, Baillie J, DeWitt J, Vege SS, American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108(9):1400-15; 1416. doi: 10.1038/ajg.2013.218.
- Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation 1999;99(22):2901-7. doi: 10.1161/01.cir.99.22.2901.
- Wright WT, Young IS, Nicholls DP, Graham CA. Genetic screening of the LPL gene in hypertriglyceridaemic patients. Atherosclerosis 2008;199(1):187-92. doi: 10.1016/j.atherosclerosis.2007.10.029.
- Monsalve MV, Henderson H, Roederer G, et al. A missense mutation at codon 188 of the human lipoprotein lipase geneis a frequent cause of lipoprotein lipase deficiency in persons ofdifferent ancestries. J Clin Invest 1990;86(3):728-34. doi: 10.1172/JCI114769.
- Hata A, Ridinger DN, Sutherland SD, et al. Missense mutations in exon 5 of the human lipoprotein lipase gene: inactivation correlates with loss of dimerization. J Biol Chem 1992;267(8):20132-9. PMID: 1400331. doi: 10.1016/S0021-9258(19)88676-3.
- Ooi EMM, Russell BS, Olson E, et al. Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations. Arterioscler Thromb Vasc Biol 2012;32(2):459-66. doi:10.1161/ATVBAHA.111.238493.
- Dron JS, Wang J, Cao H, et al. Severe hypertriglyceridemia is primarily polygenic. J Clin Lipidol 2019;13(1):80-8. doi: 10.1016/j.jacl.2018.10.006.
- Dron JS, Hegele RA. Polygenic influences on dyslipidemias. Curr Opin Lipidol 2018;29(2):133-43. doi: 10.1097/MOL.0000000000000482
- Carr RA, Rejowski BJ, Cote GA, Pitt HA, Zyromski NJ. Systematic review of hypertriglyceridemia-induced acute pancreatitis: a more virulent etiology? Pancreatology 2016;16(4):469-76. doi: 10.1016/j.pan.2016.02.011.
- Amblee A, Mohananey D, Morkos M, et al. Acute Pancreatitis in Patients with Severe Hypertriglyceridemia in a Multi-Ethnic Minority Population. Endocr Pract 2018;24(5):429-36. doi: 10.4158/EP-2017-0178.
- Sandhu S, Al-Sarraf A, Taraboanta C, Frohlich J, Francis GA. Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study. Lipids Health Dis 2011;10:157. doi: 10.1186/1476-511X-10-157.
- Schaap-Fogler M, Schurr D, Schaap T, Leitersdorf E, Rund D. Long-term plasma exchange for severe refractory hypertriglyceridemia: a decade of experience demonstrates safety and efficacy. J Clin Apher 2009;24(6):254-8. doi: 10.1002/jca.20224.
- Padmanabhan A, Connelly-Smith L, Aqui N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher 2019;34(3):171-354. doi: 10.1002/jca.21705.
- Zhang XL, Li F, Zhen YM, Li A, Fang Y. Clinical Study of 224 Patients with Hypertriglyceridemia Pancreatitis. Chin Med J (Engl) 2015;128(15):2045-9. doi: 10.4103/0366-6999.161361
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 12 Aralık 2022 |
| Gönderilme Tarihi | 10 Nisan 2022 |
| Yayımlandığı Sayı | Yıl 2022 |