Lack of association between vitamin D and calcitonin receptor gene polymorphisms and forearm bone values of young Greek males.

UNLABELLED: INTRODUCTION--HYPOTHESIS: Since the genetic bases of bone mass regulation in males are still poorly understood and the role of calciotropic hormones on bone mineral metabolism is absolute, our hypothesis is based on the certainty that specific genetic polymorphism will contribute, at least, on bone mass values. Our objective was to examine the relative contribution of genetic variables to the regulation of bone values in a population of young healthy men, focusing on the BsmI polymorphism of vitamin D receptor (VDR) gene and the AluI polymorphism of calcitonin receptor (CTR) gene. METHODS: Areal bone mineral density (aBMD), bone mineral content (BMC) and geometrical areas at specific skeletal sites of the forearm, of 301 healthy Caucasian young men, aged 18-25, were assessed by single X-ray absorptiometry (Osteometer DTX-100). VDR and CTR alleles were determined by BsmI and AluI endonuclease restriction fragment analyses. Analysis of covariance was used as a statistical model. RESULTS: No significant differences in the forearm aBMD, BMC or in area values were observed between the VDR and CTR genotypes. Findings did not change after adjusting for demographic characteristics. CONCLUSIONS: The BsmI and AluI polymorphisms are not related to the forearm bone values either reflecting mass or geometrical variables in this male population.

Lifestyle factors and forearm bone density in young Greek men.

OBJECTIVE: The aim of this study was to evaluate the effects of dietary factors (calcium, proteins, alcohol, coffee and tea intake), exercise, sunlight exposure and immobilization on bone mineral content (BMC) and bone mineral density (BMD) in young men. PATIENTS AND MEASUREMENTS: We examined a group of 300 healthy men, aged 18-30. Mean weight was 80-81 kg (53-125 kg range) and height 179 cm (160-195 cm range). Distal BMC (dBMC), distal BMD (dBMD) and ultradistal BMD (udBMD) at the radius were measured by single X-ray absorptiometry (Osteometer DTX). The data concerning lifestyle factors were obtained through a questionnaire. The 300 men were divided in four groups according to calcium intake, four groups taking into account protein and three groups alcohol intake. There also were five groups of exercise level, six groups of sun exposure and two groups of duration of immobilization. RESULTS: In the group with the lowest levels of calcium intake (< 400 mg/day), dBMD and udBMD were lower than in the other groups of calcium intake (P = 0.002). dBMC and udBMD were lower (P = 0.043 and 0.015, respectively) in subjects with low physical activity (< 2 h/week), whereas dBMC and udBMD were higher (P < 0.0005) in subjects with frequent sun exposure (group labelled 'very often'). Multiple regression analysis on bone mineral density of the forearm showed that, calcium intake, exercise and sunlight were also independent predictors of bone mass. No significant correlation between the other examined factors and BMD or BMC was detected. CONCLUSIONS: Calcium intake, exercise level and sun exposure showed a statistically significant correlation with distal BMD and BMC in young adult men.

Molecular insights into the immunopathogenesis of follicular lymphoma.

Follicular lymphoma is caused by the transformation of a germinal-center-derived B cell with a t(14;18) chromosomal translocation. The distribution of somatic mutations within immunoglobulin genes indicates that follicular-lymphoma cells can interact with antigen. In addition, nonimmunoglobulin genes such as BCL6 seem to undergo somatic hypermutation. Here, Kostas Stamatopoulos and colleagues relate the molecular data about immunoglobulin genes and the protooncogenes BCL2 and BCL6 to the pathogenesis and evolution of follicular lymphoma.

Molecular analysis of bcl-1/IgH junctional sequences in mantle cell lymphoma: potential mechanism of the t(11;14) chromosomal translocation.

Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation that juxtaposes the bcl-1 locus to immunoglobulin (Ig) gene sequences and leads to deregulation of cyclin D1 gene. t(11;14) is thought to result from an error of the recombinase during D-JH Ig gene assembly; however, data on the underlying mechanism and candidate recombination-targeting motifs in the major translocation cluster (MTC) of the bcl-1 gene are lacking. bcl-1/IgH junctional sequences from seven MCL patients were amplified by PCR using primers targeting MTC and JH sequences on chromosomes 11q13 and 14q32, respectively. PCR products were directly sequenced and junctional sequences were searched for homology to known germline D genes. bcl-t MTC breakpoints were searched for the presence of possible recombination target motifs; heptamers, nonamers, binding sequence of the bp45 nuclease, x-like sequences and D gene segments. bcl-1/JH junctions were found to bear homology to D gene segments (DLR3, DM and DIR5) in 3/7 MCL samples. A computer-based search in previously published and/or submitted to GenBank bcl-1/JH junctional sequences identified homology to D genes in 1/4 MCL tumour samples and 1/4 MCl cell lines; DXP4 or D23/7 and DHQ52 or D22/21 or DXP5, respectively. The MTC locus contained motifs with homology to bp45 nuclease binding sequence, x-like sequences, heptamers/nonamers, D-like DIR genes and non-homologous recombination short (6 bp) DNA sequences. The above data indicate that the t(11;14) translocation in MCL may also occur at a more mature stage of B-cell ontogeny than previously thought, i.e. during VH-to-DJH rearrangement. Various known recombination motifs within MTC may contribute to an illegitimate recombination event between bcl-1 and DJH.