Phospho- and sphingolipid metabolism is altered in hereditary hemochromatosis independent of iron content and PNPLA3 polymorphism

Background:

Studies have reported inconsistent effects of iron in lipid metabolism.

Objective:

The objective of this study was to investigate the relationship between lipid metabolism including neutral and polar lipids according to iron status and PNPLA3 polymorphism (rs738409/I148 M) in hereditary hemochromatosis (HH).

Methods:

We conducted a cohort study of 34 subjects with HH and 10 healthy subjects. Patients were analyzed for their iron status including iron, ferritin, transferrin and transferrin saturation and serum lipid profile including lipoproteins, neutral and polar lipids. Contents of phospho- and sphingolipids were determined by a triple-quadrupole Micro Mass Quattro Premier coupled with liquid-chromatography. For subgroup analysis, subjects with HH were subgrouped into low ferritin (< 300 µg/l) and high ferritin (> 300 µg/l).

Results:

Triglycerides were significantly higher in high vs. low HH ferritin group and vs. healthy controls. AST and ALT were significantly elevated in high ferritin group compared to low ferritin group and healthy controls. Analysis of serum phospho- and sphingolipids showed significantly lower PC in HH compared to control group irrespective of ferritin levels. PE was significantly higher and PC/PE ratio was clearly lower in HH group compared to control group. More patients in high ferritin group had pronounced steatosis (83.3%) compared to low ferritin group (64.7%). Analysis of PNPLA3 polymorphism revealed a positive correlation with serum triglycerides, frequency and severity of hepatic steatosis in particular in high ferritin group. Alterations in serum phospho- and sphingolipids did not correlate with PNPLA3 polymorphism in HH.

Conclusion:

When compared to healthy controls subjects with HH showed disturbances in phospho- and sphingolipid metabolism, especially of PC and PE, irrespective of their ferritin levels. In addition, HH patients with high ferritin levels showed significantly increased triglycerides when compared to HH patients with low ferritin and when compared to healthy controls.