PMID- 38293718
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240325
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Linking)
VI  - 44
IP  - 4
DP  - 2024 Apr
TI  - Impact of PNPLA3 and TM6SF2 polymorphisms on the prognosis of patients with MASLD 
      and type 2 diabetes mellitus.
PG  - 1042-1050
LID - 10.1111/liv.15845 [doi]
AB  - BACKGROUND/AIMS: Longitudinal studies assessing the impact of genetic 
      polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and 
      Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are scarce. This 
      study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic 
      and extrahepatic outcomes in T2DM-MASLD individuals. METHODS: Patients' 
      polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and 
      CT + TT; combined comparing no mutant allele, one allele G or T or >/=2 alleles G 
      or T. Hierarchical models were built to assess associations between polymorphisms 
      and outcomes, independently of confounding factors. Multivariate logistic 
      regression was used for cirrhosis and its complications and extrahepatic cancer, 
      and Cox regression for cardiovascular events (CVEs) and all-cause mortality. 
      RESULTS: In total, 407 T2DM-MASLD patients (62.1 +/- 10.5 years, 67.6% women) were 
      followed for 11 (6-13) years. Having at least one G or T allele independently 
      increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. 
      Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if 
      two or more risk alleles were present (OR 18.48; 95% CI 6.15-55.58; p < .001). 
      Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 
      CT + TT, also with an even higher risk when two or more risk alleles were present 
      in the combined evaluation (OR 27.20; 95% CI 5.26-140.62; p < .001). There were 
      no associations with CVEs or mortality outcomes. CONCLUSION: In T2DM, PNPLA3 and 
      TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an 
      increased risk of cirrhosis and its complications.
CI  - (c) 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Lavrado, Natalia Coelho
AU  - Lavrado NC
AUID- ORCID: 0009-0000-6250-6355
AD  - Internal Medicine Post Graduate Program, Medical School, Federal University of 
      Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Salles, Gil Fernando
AU  - Salles GF
AUID- ORCID: 0000-0001-6318-7077
AD  - Department of Internal Medicine, Medical School, Federal University of Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - Cardoso, Claudia Regina Lopes
AU  - Cardoso CRL
AUID- ORCID: 0000-0002-4909-0153
AD  - Department of Internal Medicine, Medical School, Federal University of Rio de 
      Janeiro, Rio de Janeiro, Brazil.
FAU - de Franca, Paulo Henrique Condeixa
AU  - de Franca PHC
AUID- ORCID: 0000-0002-1750-9132
AD  - Laboratory of Molecular Biology, Medicine Department, University of Joinville 
      Region - UNIVILLE, Joinville, Brazil.
FAU - Melo, Maria Fernanda Di Guimaraes Goncalves
AU  - Melo MFDGG
AUID- ORCID: 0009-0007-8599-310X
AD  - Medical School, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Leite, Nathalie Carvalho
AU  - Leite NC
AUID- ORCID: 0000-0001-9066-0405
AD  - Division of Hepatology, Clementino Fraga Filho University Hospital, Federal 
      University of Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Villela-Nogueira, Cristiane Alves
AU  - Villela-Nogueira CA
AUID- ORCID: 0000-0003-1355-2368
AD  - Department of Internal Medicine, Medical School, Federal University of Rio de 
      Janeiro, Rio de Janeiro, Brazil.
LA  - eng
GR  - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)/
GR  - Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/
GR  - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES)/
PT  - Journal Article
DEP - 20240131
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (TM6SF2 protein, human)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Humans
MH  - Female
MH  - Male
MH  - *Diabetes Mellitus, Type 2/complications/genetics
MH  - Genetic Predisposition to Disease
MH  - Polymorphism, Single Nucleotide
MH  - *Fatty Liver
MH  - Liver Cirrhosis/genetics
MH  - Fibrosis
MH  - Prognosis
MH  - *Non-alcoholic Fatty Liver Disease/genetics
MH  - Genotype
MH  - Membrane Proteins/genetics
OTO - NOTNLM
OT  - PNPLA3
OT  - TM6SF2
OT  - genetic polymorphisms
OT  - metabolic dysfunction-associated steatotic liver disease
OT  - prognosis
OT  - type 2 diabetes mellitus
EDAT- 2024/01/31 06:42
MHDA- 2024/03/25 06:42
CRDT- 2024/01/31 04:35
PHST- 2023/12/28 00:00 [revised]
PHST- 2023/11/29 00:00 [received]
PHST- 2024/01/05 00:00 [accepted]
PHST- 2024/03/25 06:42 [medline]
PHST- 2024/01/31 06:42 [pubmed]
PHST- 2024/01/31 04:35 [entrez]
AID - 10.1111/liv.15845 [doi]
PST - ppublish
SO  - Liver Int. 2024 Apr;44(4):1042-1050. doi: 10.1111/liv.15845. Epub 2024 Jan 31.