br Conclusion In white Flemish

Conclusion In white Flemish and black South Africans recruited from the general population, eGFR decreased and the risk of renal impairment increased with higher dp-ucMGP, a marker of vitamin K deficiency. These epidemiological findings support the concept that active MGP might not only inhibit calcification in large arteries, as was well known before (Knapen et al., 2015), but might also protect renal function. Our observations potentially highlight new avenues for promoting renal health, for instance by increasing the dietary intake of vitamin K either by supplementation or by increasing the intake of nutrients rich in vitamin K.
Funding The European Union (HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-F7-305507 HOMAGE and the European Research Council Advanced Researcher Grant-2011-294713-EPLORE) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish community, Brussels, Belgium (G.0881.13, G.088013 and 11Z0916N) currently support the Studies Coordinating Centre in Leuven. Furthermore, the South African Study received funding from the South African National Research Foundation (GUN 2073040), the Medical Research Council of South Africa, and the Africa Unit for Transdisciplinary Health Research (AUTHeR) of the North-West University (Potchefstroom Campus).
Role of sponsors
Author Contributions
Conflict of Interest
Acknowledgments
Introduction Niemann Pick type C (NP-C) is a neurovisceral disease that is caused by an impaired intracellular transport of cholesterol and D-Luciferin Supplier based on mutations in the NPC1 or NPC2 gene (Carstea et al., 1997; Naureckiene et al., 2000). NP-C is underdiagnosed and not readily identifiable due to a variable age of onset and a variety of age-dependent symptoms. Whereas younger patients present primarily with visceral symptoms such as hepatosplenomegaly followed by progressive intellectual and neurological deterioration, adults often develop psychiatric problems, including depression and psychosis (reviewed by Patterson et al., 2012; Mengel et al., 2013). Due to the heterogeneous clinical phenotype, diagnosis is often delayed for many years or missed altogether. Since a disease modifying therapy is available (Patterson et al., 2007) and more are being developed, there is an urgent need for a reliable and robust biomarker. Interruption of cholesterol transport leads to an increased non-enzymatic oxidation of a very small fraction of the accumulated cholesterol in NP-C cells. The oxidation products of cholesterol, called oxysterols, can be measured by GC–MS or LC–MS/MS in human plasma. It has been shown that 7-ketocholesterol (7-KC) and cholestane-3β,5α,6β-triol (c-triol), are elevated in the plasma of NP-C1 and NP-C2 patients (Porter et al., 2010; Boenzi et al., 2014; Reunert et al., 2015; Jiang et al., 2011). In a large scale investigator-initiated study, we evaluated c-triol as a potential biomarker for the diagnosis of Niemann Pick type C disease. Using GC–MS, 1902 plasma samples of patients with the suspicion of NP-C disease, carriers of a heterozygous mutation in the NPC1 gene and confirmed NP-C patients were analyzed.
Material and Methods
Results Within three years (2012–2014), cholestane-3β,5α,6β-triol was measured in 1902 plasma samples of patients with suspected NP-C disease (Fig. 1). 1704 samples had a normal c-triol concentration.
Discussion The lack of appropriate biomarkers for the diagnosis of Niemann Pick type C leads to an underestimation of the incidence of this disease which is thought to be 1:120,000–150,000 in Western Europeans (Vanier and Millat, 2003). Indeed, Wassif et al. (2015) estimated the combined incidence of NP-C1 and NP-C2 as 1:89,000. In the current study, 71 new NP-C patients were diagnosed by oxysterol analysis followed by genetic analysis in a time frame of three years (2012–2014). Additionally, seven NP-C patients were identified by genetic analysis combined with filipin staining or high clinical suspicion. 25% of the heterozygote carriers (6/24) had c-triol levels above the cut-off value. This is exactly the same frequency of positive carriers as reported by Jiang et al. (2011) which shows the consistency of the assay across different platforms and centers.