Interaction between estrogen receptor-α and PNPLA3 p.I148M variant drives fatty liver disease susceptibility in women.

ABSTRACT: Fatty liver disease (FLD) caused by metabolic dysfunction is the leading cause of liver disease and the prevalence is rising, especially in women. Although during reproductive age women are protected against FLD, for still unknown and understudied reasons some develop rapidly progressive disease at the menopause. The patatin-like phospholipase domain-containing 3 (PNPLA3) p.I148M variant accounts for the largest fraction of inherited FLD variability. In the present study, we show that there is a specific multiplicative interaction between female sex and PNPLA3 p.I148M in determining FLD in at-risk individuals (steatosis and fibrosis, P < 10^-10; advanced fibrosis/hepatocellular carcinoma, P = 0.034) and in the general population (P < 10^-7 for alanine transaminase level

SUBMITTER: Cherubini A 

PROVIDER: S-EPMC10579099 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature