Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

Abstract

Genome-Wide Association Study (GWAS) Higher Blood pressure Arthritides Neuropsychiatric conditions Malignancies Lower Anaemias Lipidaemias Ischaemic heart disease Genetically higher central obesity Highlights Variants in HFE and TMPRSS6 are associated with higher liver iron. There is genetic evidence that higher central obesity causes higher liver iron. Liver iron variants are not organ specific and associate with multiple diseases.

Uncovering the genetics of cirrhosis: New plots for the usual suspects

“…The novelty of the study by Chen et al extended to the evaluation of the impact of risk variants on non liver‐related traits. In line with independent findings, both the HFE and SERPINA1 variants decreased circulating lipids, thereby possibly contributing to fatty liver by inducing endoplasmic reticulum stress and impairment of lipoprotein secretion …”

“…However, this interpretation is consistent with new evidence indicating that heterozygous carriage of HFE p.C282Y and SERPINA1 p.E342K variants, previously deemed as autosomal recessive traits, favours liver disease . In addition, hepatic fat has recently emerged as a major determinant of iron stores by facilitating iron absorption, especially in carriers of HFE p.C282Y and SERPINA1 p.E342K . Chen et al also highlighted that HFE p.C282Y favours haemoglobinization, thereby protecting against iron deficiency and anaemia, which might have provided an evolutionary advantage to carriers .…”

“…Concerning other mechanisms of liver damage, data suggest that even the mild hepatic iron accumulation typically favoured by carriage of HFE p.C282Y predisposes to cirrhosis. Confirmation of the impact on liver outcomes in participants stratified by genotypic data, concurrent risk factors, and iron status is still required.…”

“…In addition, hepatic fat has recently emerged as a major determinant of iron stores by facilitating iron absorption, especially in carriers of HFE p.C282Y and SERPINA1 p.E342K . Chen et al also highlighted that HFE p.C282Y favours haemoglobinization, thereby protecting against iron deficiency and anaemia, which might have provided an evolutionary advantage to carriers . An intriguing finding was that cirrhosis risk variants in PNPLA3 , TM6SF2 and HSD17B13 were also associated with higher haemoglobin levels, as well as with other blood traits.…”

Multiparametric MR mapping in clinical decision-making for diffuse liver disease

“…Genetic testing is required to differentiate true genetic hemochromatosis (homozygous C282Y) from the other forms of milder hemochromatosis or even secondary iron overload syndromes [22,119]. Recent studies have identified elevated iron without homozygosity for the p.C282Y variant in the HFE gene, highlighting the continued undetected disease existing in the general population [120][121][122]. Increased iron can be co-existing in NAFLD, ALD and other chronic liver diseases [22,122,123].…”