Genetic
LCAT deficiency is a rare recessive autosomal disease due to loss-of-function mutations in the gene coding for the
enzyme lecithin:cholesterol acyltransferase (LCAT). Homozygous carriers are characterized by
corneal opacity,
haemolytic anaemia and renal disease, which represent the first cause of morbidity and mortality in these subjects. Diagnostic and prognostic markers capable of early detecting declining kidney function in these subjects are not available, and the specific serum or urine proteomic signature of LCAT deficient carriers has never been assessed. Taking advantage of a proteomic approach, we performed 2-DE analysis of carriers' plasma and identified
proteins present at different concentration in samples from homozygous carriers. Our data confirm the well-known alterations in the concentration of circulating
apolipoproteins, with a statistically significant decrease of both
apoA-I and
apoA-II and a statistically significant increase of
apoC-III. Furthermore, we observed increased level of alpha-1-antitrypsin, zinc-alpha-2-glycoprotein and
retinol-binding protein 4, and reduced level of
clusterin and
haptoglobin. Interestingly, only beta but not alpha subunit of
haptoglobin is significant reduced in homozygous subjects. Despite the limited sample size, our findings set the basis for assessing the identified
protein in a larger population and for correlating their levels with
clinical markers of renal function and anaemia. SIGNIFICANCE: This investigation defines the effects of
LCAT deficiency on the level of the major
plasma proteins in homozygous and heterozygous carriers. Increase for some
proteins, with different function, together with a drop for
haptoglobin, and specifically for
haptoglobin beta chains, are reported for the first time as part of a coherent signature. We are glad to have the opportunity to report our findings on this subject, which is one of the main interests for our research group, when Journal of Proteomics celebrates its 10th anniversary. With its various sections devoted to different areas of research, this journal is a privileged forum for publishing proteomic investigations without restrictions either in sample type or in technical approach. It is as well a privileged forum for reviewing literature data on various topics related to proteomics investigation, as colleagues in our research group have done over the years; by the way, a good share of the reviewed papers were as well reports published in Journal of Proteomics itself. The journal also offers opportunities for focused surveys through thematic issues devoted to a variety of subjects, timely selected for their current relevance in research; it was an honour for colleagues in our group to recently act as editors of one of those. Out of this diverse experience, we express our appreciation for the endeavour of Journal of Proteomics in its first 10 years of life - and wish identical and possibly greater success for the time to come.