A rare genetic variant in the manganese transporter SLC30A10 and elevated liver enzymes in the general population.
Biliary tract cancer
Cholangiocarcinoma
Cirrhosis
Epidemiology
General population
Hypermanganesemia
Magnetic resonance spectroscopy
NAFLD
PNPLA3
UK Biobank
Journal
Hepatology international
ISSN: 1936-0541
Titre abrégé: Hepatol Int
Pays: United States
ID NLM: 101304009
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
06
12
2021
accepted:
14
03
2022
pubmed:
10
4
2022
medline:
10
6
2022
entrez:
9
4
2022
Statut:
ppublish
Résumé
A genetic variant in the manganese transporter SLC30A10 (rs188273166, p.Thr95Ile) was associated with increased plasma alanine transaminase (ALT) in a recent genome-wide association study in the UK Biobank (UKB). The aims of the present study were to test the association of rs188273166 with ALT in an independent cohort, and to begin to assess the clinical, hepatic, and biochemical phenotypes associated with the variant. We included n = 334,886 white participants from UKB, including 14,462 with hepatic magnetic resonance imaging (MRI), and n = 113,612 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study combined. Genotyping SLC30A10 p.Thr95Ile identified 816 heterozygotes in the UKB and 111 heterozygotes in the Copenhagen cohort. Compared to noncarriers, heterozygotes had 4 and 5 U/L higher levels of ALT in the UKB and Copenhagen cohort, respectively, and 3 U/L higher plasma aspartate transaminase and gamma-glutamyl transferase in the UKB. Heterozygotes also had higher corrected T1 on liver MRI, a marker of hepatic inflammation (p = 4 × 10 SLC30A10 p.Thr95Ile was associated with elevated liver enzymes in two large general population cohorts, and with MRI-quantified hepatic inflammation. A rare genetic variant (p.Thr95Ile) in the manganese transporter SLC30A10 is associated with elevated plasma alanine transaminase (ALT) and higher corrected T1 on liver MRI, markers of liver inflammation. These data support that the variant may increase the risk of liver disease.
Sections du résumé
BACKGROUND
BACKGROUND
A genetic variant in the manganese transporter SLC30A10 (rs188273166, p.Thr95Ile) was associated with increased plasma alanine transaminase (ALT) in a recent genome-wide association study in the UK Biobank (UKB). The aims of the present study were to test the association of rs188273166 with ALT in an independent cohort, and to begin to assess the clinical, hepatic, and biochemical phenotypes associated with the variant.
METHODS
METHODS
We included n = 334,886 white participants from UKB, including 14,462 with hepatic magnetic resonance imaging (MRI), and n = 113,612 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study combined.
RESULTS
RESULTS
Genotyping SLC30A10 p.Thr95Ile identified 816 heterozygotes in the UKB and 111 heterozygotes in the Copenhagen cohort. Compared to noncarriers, heterozygotes had 4 and 5 U/L higher levels of ALT in the UKB and Copenhagen cohort, respectively, and 3 U/L higher plasma aspartate transaminase and gamma-glutamyl transferase in the UKB. Heterozygotes also had higher corrected T1 on liver MRI, a marker of hepatic inflammation (p = 4 × 10
CONCLUSIONS
CONCLUSIONS
SLC30A10 p.Thr95Ile was associated with elevated liver enzymes in two large general population cohorts, and with MRI-quantified hepatic inflammation. A rare genetic variant (p.Thr95Ile) in the manganese transporter SLC30A10 is associated with elevated plasma alanine transaminase (ALT) and higher corrected T1 on liver MRI, markers of liver inflammation. These data support that the variant may increase the risk of liver disease.
Identifiants
pubmed: 35397106
doi: 10.1007/s12072-022-10331-w
pii: 10.1007/s12072-022-10331-w
doi:
Substances chimiques
Cation Transport Proteins
0
SLC30A10 protein, human
0
Manganese
42Z2K6ZL8P
Alanine Transaminase
EC 2.6.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
702-711Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Diabetes UK
ID : 17/0005594
Pays : United Kingdom
Organisme : Det Frie Forskningsråd
ID : 9060-00012B
Informations de copyright
© 2022. Asian Pacific Association for the Study of the Liver.
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