Influence of Type 2 Diabetes in the Association of PNPLA3 rs738409 and TM6SF2 rs58542926 Polymorphisms in NASH Advanced Liver Fibrosis
Gabriel-Medina, Pablo (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ferrer Costa, Roser (Vall d'Hebron Institut de Recerca (VHIR))
Rodríguez Frías, Francisco (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ciudin, Andreea (Vall d'Hebron Institut de Recerca (VHIR))
Augustin Recio, Salvador (Vall d'Hebron Institut de Recerca (VHIR))
Rivera Esteban, Jesús (Vall d'Hebron Institut de Recerca (VHIR))
Pericàs, Juan M. (Vall d'Hebron Institut de Recerca (VHIR))
Martínez Selva, David (Vall d'Hebron Institut de Recerca (VHIR))

Date:	2022
Abstract:	Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in western countries. Insulin resistance (IR), type 2 diabetes (T2D), and the polymorphisms patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 are independent risk factors of NASH. Nevertheless, little is known about the interaction between IR and T2D with these polymorphisms in the pathogenesis of NASH and the development of advanced fibrosis. Thus, our study aimed to investigate this relationship. This is a cross-sectional study including NASH patients diagnosed by liver biopsy, at the Vall d'Hebron University Hospital. A total of 140 patients were included (93 T2D, 47 non-T2D). T2D (OR = 4. 67; 95%CI 2. 13-10. 20; p < 0. 001), PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms (OR = 3. 94; 95%CI 1. 63-9. 54; p = 0. 002) were independently related with advanced liver fibrosis. T2D increased the risk of advance fibrosis on top of the two polymorphisms (OR = 14. 69; 95%CI 3. 03-77. 35; p = 0. 001 for PNPLA3 rs738409 and OR = 11. 45; 95%CI 3. 16-41. 55; p < 0. 001 for TM6SF2 rs58542926). In non-T2D patients, the IR (HOMA-IR ≥ 5. 2, OR = 14. 33; 95%CI 2. 14-18. 66; p = 0. 014) increased the risk of advanced fibrosis when the polymorphisms were present (OR = 19. 04; 95%CI 1. 71-650. 84; p = 0. 042). The T2D and IR status increase the risk of advanced fibrosis in patients with NASH carrying the PNPLA3 rs738409 and/or TM6SF2 rs58542926 polymorphisms, respectively.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Advanced fibrosis ; Homeostatic model assessment for insulin resistance (HOMA-IR) ; Nonalcoholic steatohepatitis (NASH) ; PNPLA3 p.I148M ; TM6SF2 p.E167K ; Type 2 diabetes (T2D)
Published in:	Biomedicines, Vol. 10 (april 2022) , ISSN 2227-9059

DOI: 10.3390/biomedicines10051015
PMID: 35625751

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