Combined effects of the TM6SF2 rs58542926, PNPLA3 rs738409 and MBOAT7 rs641738 variants on NAFLD severity: multicentre biopsy-based study

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Erscheinungsjahr:
2017
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Beschreibung:
  • BACKGROUND AND AIMS: The PNPLA3 p.I148M and TM6SF2 p.E167K and MBOAT7 rs641738 variants represent genetic risk factors for non-alcoholic fatty liver disease (NAFLD). Here we investigate if these polymorphisms modulate both steatosis and fibrosis in NAFLD patients.

    PATIENTS AND METHODS: We recruited 515 patients with NAFLD (age 16-88 years, 280 females). In 320 patients liver biopsies were performed. PCR-based assays were used to genotype the PNPLA3, TM6SF2, and MBOAT7 variants.

    RESULTS: Carriers of the PNPLA3 and TM6SF2 risk alleles showed increased serum AST and ALT activities (P<0.05). The PNPLA3 genotype was associated with steatosis grades S2-S3 (P<0.001) and fibrosis stages F2-F4 (P<0.001). The TM6SF2 genotype was associated with steatosis (P=0.003) but not with fibrosis (P>0.05). The MBOAT7 variant was solely associated with increased fibrosis (P=0.046). In the multivariate model, variants PNPLA3 (P=0.003) and TM6SF2 (P=0.030) were associated with steatosis. Fibrosis stages were affected by the PNPLA3 (P=0.042) and MBOAT7 (P=0.021), but not by the TM6SF2 polymorphism (P>0.05).

    CONCLUSIONS: The PNPLA3, TM6SF2 and MBOAT7 variants are associated with increased liver injury. The TM6SF2 variant seems to modulate predominantly hepatic fat accumulation whereas the MBOAT7 polymorphism is linked to fibrosis. The PNPLA3 polymorphism confers risk of both increased steatosis and fibrosis.

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  • info:eu-repo/semantics/restrictedAccess
Quellsystem:
Forschungsinformationssystem des UKE

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oai:pure.atira.dk:publications/17ff1633-69b9-4a1f-afa7-8e3845c1736c