Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE

Hegele, Robert; Toth, Peter; YILDIRIM SIMSIR, ILGIN; bayram, fahri; Onay, Huseyin; Abedi, Amir Hossein; Özgür, Su; McIntyre, Adam

doi:10.5543/tkda.2022.98544

Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE

Ilgın YILDIRIM ŞİMŞİR, (Ege Üniversitesi, Tıp Fakültesi, Endokrinoloji ve Metabolizma Hastalıkları Anabilim Dalı, İzmir, Türkiye)

Fahri BAYRAM, (Erciyes Üniversitesi, Tıp Fakültesi, Endokrinoloji ve Metabolizma Hastalıkları Anabilim Dalı, Kayseri, Türkiye)

Hüseyin ONAY, (Ege Üniversitesi, Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, İzmir, Türkiye)

Su ÖZGÜR, (Ege Üniversitesi, Tıp Fakültesi, Biyoistatistik ve Tıbbi Bilişim Bölümü, İzmir, Türkiye)

Adam McIntyre, (Western University, Schulich School of Medicine, Robarts Research Institute, London Ontario, Canada)

Peter Toth, (Johns Hopkins University, School of Medicine, Cicarrone Center for the Prevention of Cardiovascular Disease, Baltimore, United States of America)

Robert Hegele, (Western University, Schulich School of Medicine, Robarts Research Institute, London Ontario, Canada)

Amir Hossein ABEDİ (Erciyes Üniversitesi, Tıp Fakültesi, İç Hastalıkları Bölümü, Kayseri,Türkiye)

Türk Kardiyoloji Derneği Arşivi

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Yıl: 2023 Cilt: 51 Sayı: 1 Sayfa Aralığı: 10 - 21 Metin Dili: İngilizce DOI: 10.5543/tkda.2022.98544 İndeks Tarihi: 11-05-2023

Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE

Öz:

Objective: High triglyceride (TG) levels are associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD) and pancreatitis. The objectives for this study were to evaluate for the coexistence of severe HTG and pancreatitis in two different geographic regions of Turkey and to identify rare variants that cause monogenic HTG in our country. Methods: In our study from 2014 to 2019, patients with severe HTG who presented to the endocrinology outpatient clinics with TG levels >500 mg/dL (5.7 mmol/L) were evaluated. The LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE genes were sequenced using next generation sequencing to screen for potentially pathogenic variants. Results: Potentially pathogenic variants were identified in 64 (47.1%) of 136 patients. Variants in LPL were seen in 42 (30.9%) cases, APOA5 variants in 10 (7.4%) cases, APOC2 variants in 5 (3.7%) cases, LMF1 variants in 5 (3.7%) cases, and APOE mutations in 2 (1.5%) cases. In the subgroup that experienced pancreatitis (n = 76, 56.3%), LPL variants were seen at higher frequency (P <0.001) than in the subgroup with no history of pancreatitis (n = 60, 43.7%). Patients who developed pancreatitis (56.3%) demonstrated a median TG of 2083 mg/dL (23.5 mmol/L), and patients without pancreatitis (43.7%) demonstrated a median TG of 1244.5 mg/dL (14.1 mmol/L) (P <0.001). Conclusion: Accurate approach to HTG diagnosis is important for the prevention of pancreatitis and ASCVD. Evaluation of variants in primary HTG after excluding secondary causes may help provide a patient-centric precision treatment plan.

Anahtar Kelime:

Ciddi Hipertrigliseridemi ile İlişkili Genetik Varyantlar: LPL, APOC2, APOA5, GPIHBP1, LMF1 ve APOE

Öz:

Amaç: Yüksek trigliserid (TG) düzeyleri; aterosklerotik kardiyovasküler hastalık (ASKVH) ve pankreatit riskinde artma ile ilişkilidir. Amacımız, Türkiye'nin iki farklı coğrafi bölgesinde ciddi hipertrigliseridemi (HTG) ve pankreatit birlikteliğini değerlendirmek ve ülkemizdeki monogenik HTG’ye yol açan varyantları tanımlamaktır. Yöntemler: Çalışmamızda 2014-2019 yıllarında endokrinoloji polikniklerine başvuran, TG dü- zeyi ≥500 mg/dL (5,7 mmol/L) olan HTG vakaları incelenmiştir. LPL, APOC2, APOA5, GPIHBP1, LMF1 ve APOE genleri, potansiyel olarak patojenik varyantları taramak için yeni nesil dizileme kullanılarak sekanslanmıştır. Bulgular: Yüz otuz altı hastanın 64'ünde (%47,1) potansiyel olarak patojenik varyantlar tespit edildi. 42 (%30,9) vakada LPL, 10 (%7,4) vakada APOA5, 5 (%3,7) vakada APOC2, 5 (%3,7) vakada LMF1 ve 2 (%1,5) vakada APOE varyantları saptandı. Pankreatit geçiren grupta (n = 76, %56,3) LPL varyantları, pankreatit öyküsü olmayan (n = 60, %43,7) gruba göre daha yük- sek sıklıkta (P <0,001) görüldü. Pankreatit geçiren hastaların medyan TG'si 2083 mg/dL (23,5 mmol/L) ve pankreatit geçirmeyen hastaların medyan TG'si 1244,5 mg/dL (14,1 mmol/L) idi (P <0,001). Sonuç: Pankreatit ve ASKVH’ın önlenmesi için HTG tanısına doğru bir yaklaşım önemlidir. Sekonder nedenleri dışladıktan sonra primer HTG için varyantların değerlendirilmesi, hasta merkezli hassas bir tedavi planının yapılmasına yardımcı olabilir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	YILDIRIM SIMSIR I, bayram f, Onay H, Özgür S, McIntyre A, Toth P, Hegele R, Abedi A (2023). Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. , 10 - 21. 10.5543/tkda.2022.98544
Chicago	YILDIRIM SIMSIR ILGIN,bayram fahri,Onay Huseyin,Özgür Su,McIntyre Adam,Toth Peter,Hegele Robert,Abedi Amir Hossein Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. (2023): 10 - 21. 10.5543/tkda.2022.98544
MLA	YILDIRIM SIMSIR ILGIN,bayram fahri,Onay Huseyin,Özgür Su,McIntyre Adam,Toth Peter,Hegele Robert,Abedi Amir Hossein Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. , 2023, ss.10 - 21. 10.5543/tkda.2022.98544
AMA	YILDIRIM SIMSIR I,bayram f,Onay H,Özgür S,McIntyre A,Toth P,Hegele R,Abedi A Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. . 2023; 10 - 21. 10.5543/tkda.2022.98544
Vancouver	YILDIRIM SIMSIR I,bayram f,Onay H,Özgür S,McIntyre A,Toth P,Hegele R,Abedi A Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. . 2023; 10 - 21. 10.5543/tkda.2022.98544
IEEE	YILDIRIM SIMSIR I,bayram f,Onay H,Özgür S,McIntyre A,Toth P,Hegele R,Abedi A "Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE." , ss.10 - 21, 2023. 10.5543/tkda.2022.98544
ISNAD	YILDIRIM SIMSIR, ILGIN vd. "Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE". (2023), 10-21. https://doi.org/10.5543/tkda.2022.98544

APA	YILDIRIM SIMSIR I, bayram f, Onay H, Özgür S, McIntyre A, Toth P, Hegele R, Abedi A (2023). Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. Türk Kardiyoloji Derneği Arşivi, 51(1), 10 - 21. 10.5543/tkda.2022.98544
Chicago	YILDIRIM SIMSIR ILGIN,bayram fahri,Onay Huseyin,Özgür Su,McIntyre Adam,Toth Peter,Hegele Robert,Abedi Amir Hossein Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. Türk Kardiyoloji Derneği Arşivi 51, no.1 (2023): 10 - 21. 10.5543/tkda.2022.98544
MLA	YILDIRIM SIMSIR ILGIN,bayram fahri,Onay Huseyin,Özgür Su,McIntyre Adam,Toth Peter,Hegele Robert,Abedi Amir Hossein Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. Türk Kardiyoloji Derneği Arşivi, vol.51, no.1, 2023, ss.10 - 21. 10.5543/tkda.2022.98544
AMA	YILDIRIM SIMSIR I,bayram f,Onay H,Özgür S,McIntyre A,Toth P,Hegele R,Abedi A Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. Türk Kardiyoloji Derneği Arşivi. 2023; 51(1): 10 - 21. 10.5543/tkda.2022.98544
Vancouver	YILDIRIM SIMSIR I,bayram f,Onay H,Özgür S,McIntyre A,Toth P,Hegele R,Abedi A Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE. Türk Kardiyoloji Derneği Arşivi. 2023; 51(1): 10 - 21. 10.5543/tkda.2022.98544
IEEE	YILDIRIM SIMSIR I,bayram f,Onay H,Özgür S,McIntyre A,Toth P,Hegele R,Abedi A "Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE." Türk Kardiyoloji Derneği Arşivi, 51, ss.10 - 21, 2023. 10.5543/tkda.2022.98544
ISNAD	YILDIRIM SIMSIR, ILGIN vd. "Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE". Türk Kardiyoloji Derneği Arşivi 51/1 (2023), 10-21. https://doi.org/10.5543/tkda.2022.98544