Plasma lipids in Pseudoxanthoma Elasticum (PXE) patients: A comparative study with population-based reference values and Non-PXE controls

Background and aims: – Pseudoxanthoma elasticum (PXE) is a rare genetic disease caused by pathogenic mutations in the ABCC6 gene, resulting in low values of inorganic pyrophosphate (PPi). While low PPi is thought to contribute to arterial calcification, it remains unclear whether this fully explains premature calcification in PXE. It has been hypothesized that the ABCC6 gene could be related to dyslipidemia, which could contribute to vascular calcification seen in PXE. The aim of this study is to evaluate the relation between PXE and plasma lipid concentrations in a large cohort of PXE patients compared with reference values for the general population and compared with non-PXE controls. Methods: – The plasma concentrations of total cholesterol, HDL-cholesterol, tiglycerides, and LDL-cholesterol of 312 PXE patients were compared to age- and sex-matched modeled data of the general Dutch population. Differences in median lipid levels were compared with Mann-Whitney-U test. Secondly, plasma lipid concentrations of 44 PXE patients were compared to 44 not-genetically related relatives (spouses or friends), with linear models adjusted for age, sex and BMI. Results: – Total cholesterol in PXE patients was 5.6 [IQR 4.6–6.4] mmol/L versus 5.3 [IQR 4.7–6.0] mmol/L (p < 0.01) in the general population; triglycerides were 1.1 [IQR 0.9–1.7] mmol/L versus 1.0 [0.7–1.4] mmol/L (p < 0.01); HDL-c was 1.4 [IQR 1.2–1.7] mmol/L versus 1.5 [IQR 1.2–1.8] mmol/L (p = 0.03) and LDL-c was 3.3 [IQR 2.7–4.1] mmol/L versus 3.2 [IQR 2.7–3.8] mmol/L (p = 0.01). In the patient control analysis with 44 pairs and age, sex and BMI adjusted, comparison with the non-PXE controls only triglycerides were significantly different (mean difference: 0.38 (0.13–0.63)). Conclusion: –The lipid profiles of PXE patients are marginally different from the general population or compared to a matched control group, but the differences are unlikely to be clinically relevant. It is therefore unlikely that plasma lipids contribute to the premature vascular calcifications in PXE patients.