Association of Vitamin D Receptor Gene Polymorphisms with Serum Vitamin D Levels in a Greek Rural Population (Velestino Study).

BACKGROUND/AIM: An alarming increase in vitamin D deficiency even in sunny regions highlights the need for a better understanding of the genetic background of the vitamin D endocrine system and the molecular mechanisms of gene polymorphisms of the vitamin D receptor (VDR). In this study, the serum levels of 25(OH)D3 were correlated with common VDR polymorphisms (ApaI, BsmI, FokI, and TaqI) in 98 subjects of a Greek homogeneous rural population. METHODS: 25(OH)D3 concentration was measured by ultra-HPLC, and the VDR gene polymorphisms were identified by quantitative real-time PCR followed by amplicon high-resolution melting analysis. RESULTS: Subjects carrying either the B BsmI (OR: 0.52, 95% CI: 0.27-0.99) or t TaqI (OR: 2.06, 95%: 1.06-3.99) allele presented twice the risk for developing vitamin D deficiency compared to the reference allele. Moreover, subjects carrying 1, 2, or all 3 of these genotypes (BB/Bb, Tt/tt, and FF) demonstrated 2-fold (OR: 2.04, 95% CI: 0.42-9.92), 3.6-fold (OR: 3.62, 95% CI: 1.07-12.2), and 7-fold (OR: 6.92, 95% CI: 1.68-28.5) increased risk for low 25(OH)D3 levels, respectively. CONCLUSIONS: Our findings reveal a cumulative effect of specific VDR gene polymorphisms that may regulate vitamin D concentrations explaining, in part, the paradox of vitamin D deficiency in sunny regions, with important implications for precision medicine.

Combined metabolome and transcriptome profiling provides new insights into diterpene biosynthesis in S. pomifera glandular trichomes.

BACKGROUND: Salvia diterpenes have been found to have health promoting properties. Among them, carnosic acid and carnosol, tanshinones and sclareol are well known for their cardiovascular, antitumor, antiinflammatory and antioxidant activities. However, many of these compounds are not available at a constant supply and developing biotechnological methods for their production could provide a sustainable alternative. The transcriptome of S.pomifera glandular trichomes was analysed aiming to identify genes that could be used in the engineering of synthetic microbial systems. RESULTS: In the present study, a thorough metabolite analysis of S. pomifera leaves led to the isolation and structure elucidation of carnosic acid-family metabolites including one new natural product. These labdane diterpenes seem to be synthesized through miltiradiene and ferruginol. Transcriptomic analysis of the glandular trichomes from the S. pomifera leaves revealed two genes likely involved in miltiradiene synthesis. Their products were identified and the corresponding enzymes were characterized as copalyl diphosphate synthase (SpCDS) and miltiradiene synthase (SpMilS). In addition, several CYP-encoding transcripts were identified providing a valuable resource for the identification of the biosynthetic mechanism responsible for the production of carnosic acid-family metabolites in S. pomifera. CONCLUSIONS: Our work has uncovered the key enzymes involved in miltiradiene biosynthesis in S. pomifera leaf glandular trichomes. The transcriptomic dataset obtained provides a valuable tool for the identification of the CYPs involved in the synthesis of carnosic acid-family metabolites.

Anti-La/SSB antiidiotypic antibodies in maternal serum: a marker of low risk for neonatal lupus in an offspring.

OBJECTIVE: The anti-La/SSB response to major B cell epitopes of La/SSB can be blocked by an active idiotypic/antiidiotypic network, which can be identified using synthetic complementary epitopes deduced from the sequence of the major B cell epitopes of the molecule. This study evaluated the role of this network in pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies in the development of neonatal lupus syndrome (NLS). METHODS: Sixty-three serum samples collected from anti-Ro/anti-La-positive women during pregnancy or within 6 months after delivery were obtained from the Research Registry for Neonatal Lupus and the PR Interval Dexamethasone Evaluation study. These samples, as well as 30 sera from healthy individuals, were tested in a blinded manner by enzyme-linked immunosorbent assay against synthetic peptides corresponding to major B cell epitopes and complementary epitopes of La/SSB. RESULTS: Sera from mothers giving birth to a healthy child and having no history of a child with NLS exhibited higher antiidiotypic antibody activity compared with mothers carrying a child with NLS (P < 0.0001) or mothers giving birth to a healthy child but who previously gave birth to a child with NLS (P = 0.0151). Sera from mothers of healthy children, which exhibited no apparent epitope activity against amino acids 349-364, revealed a significantly greater frequency of hidden anti-349-364aa epitope responses, blocked by antiidiotypic antibodies, as compared with sera from women pregnant with an affected child (P = 0.0094). CONCLUSION: The presence of antiidiotypic antibodies to autoantibodies against La/SSB may protect the fetus by blocking pathogenic maternal autoantibodies. Testing for these antiidiotypic responses may be useful in predicting a decreased risk of NLS.