MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis.
Adolescent
Adult
Aged
Antioxidants
/ metabolism
Child
Female
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
Genotype
Hepatitis, Autoimmune
/ complications
Humans
Liver Cirrhosis
/ etiology
Male
Middle Aged
Mitochondrial Proteins
/ genetics
Oxidoreductases
/ genetics
Phenotype
Polymorphism, Genetic
/ genetics
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 12 2021
23 12 2021
Historique:
received:
28
06
2021
accepted:
29
11
2021
entrez:
24
12
2021
pubmed:
25
12
2021
medline:
27
1
2022
Statut:
epublish
Résumé
The clinical picture of autoimmune hepatitis (AIH) varies markedly between patients, potentially due to genetic modifiers. The aim of this study was to evaluate genetic variants previously associated with fatty liver as potential modulators of the AIH phenotype. The study cohort comprised 313 non-transplanted adults with AIH. In all patients, the MARC1 (rs2642438), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926), and MBOAT7 (rs641738) variants were genotyped using TaqMan assays. Mitochondrial damage markers in serum were analyzed in relation to the MARC1 variant. Carriers of the protective MARC1 allele had lower ALT and AST (both P < 0.05). In patients treated for AIH for ≥ 6 months, MARC1 correlated with reduced AST, ALP, GGT (all P ≤ 0.01), and lower APRI (P = 0.02). Patients carrying the protective MARC1 genotype had higher total antioxidant activity (P < 0.01) and catalase levels (P = 0.02) in serum. The PNPLA3 risk variant was associated with higher MELD (P = 0.02) in treated patients, whereas MBOAT7 increased the odds for liver cancer (OR = 3.71). None of the variants modulated the risk of death or transplantation. In conclusion, the MARC1 polymorphism has protective effects in AIH. Genotyping of MARC1, PNPLA3, and MBOAT7 polymorphisms might help to stratify patients with AIH.
Identifiants
pubmed: 34949757
doi: 10.1038/s41598-021-03521-3
pii: 10.1038/s41598-021-03521-3
pmc: PMC8702547
doi:
Substances chimiques
Antioxidants
0
Mitochondrial Proteins
0
Oxidoreductases
EC 1.-
mitochondrial amidoxime reducing component 1, human
EC 1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24407Informations de copyright
© 2021. The Author(s).
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