The aim of this study is to investigate the role of single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) and of the related co-chaperone FKBP5 genes in the development of glucocorticoid (GC) resistance in Crohn's disease (CD) and ulcerative colitis (UC) patients. We have developed a high-resolution DNA melting method that allows simultaneous identification of GR (BclI, N363S and ER22/23EK) and FKBP5 (rs3800373, rs1360780 and rs4713916) polymorphisms. Genotype frequencies were determined in 100 consecutive CD and 100 UC patients under GCs therapy (50 responders and 50 resisters). The variation of FKBP5 polymorphism rs4713916 (G/A), in the putative promoter region of FKBP5, is significantly associated with resistance to GC treatment in CD (responder ¼ 17% versus resister ¼ 35%; P ¼ 0.0043). No significant differences were found in UC patients. If these preliminary findings will be confirmed, the combination of GR and FKBP5 mutational analyses could help to identify subgroups of CD patients with higher chances to benefit from GC treatment.

BackgroundThere are few data about the association between work‐related stress and the American Heart Association ideal cardiovascular health (CVH) metrics. We studied the association between work‐family conflict (WFC) and ideal CVH scores in the ELSA‐Brasil (Brazilian Longitudinal Study of Adult Health) baseline study.Methods and ResultsWe analyzed data of active workers (5424 men and 5967 women), aged 35 to 74 years, from 2008 to 2010. Ideal CVH scores were calculated based on the lifestyle and health metrics proposed by the American Heart Association, using data from questionnaires and clinical and laboratory examinations from the ELSA‐Brasil study baseline. The WFC questionnaire was based on the Frone model, validated for Brazilian Portuguese. WFC domains (time and strain‐based work interference with family, family interference with work, and lack of time for personal care and leisure) and frequency (never to rarely, sometimes, or frequently) were self‐reported. Main models were adjusted for age, sex, race, educational level, income, and study site. Positive relative predicted score differences (rPSDs) indicate higher predicted scores. We found lower lifestyle ideal CVH scores among men (rPSD, −5.7%; P=0.002) and women (rPSD, −10.2%; P<0.001) with frequent lack of time for personal care and leisure. We found lower lifestyle ideal CVH scores among women with frequent strain‐based work interference with family (rPSD, −5.1%; P=0.002), and family interference with work (rPSD, −8.6%; P=0.001). We found higher health ideal CVH scores among men with frequent WFC, which may be attributable to reverse causation.ConclusionsWe found significant associations between WFC and ideal CVH scores. These associations were heterogeneous according to sex.

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X-linked hereditary spastic paraplegias (HSPs) present with two distinct phenotypes: pure and complicated. The pure form is characterized by slowly progressive weakness and spasticity of the lower limbs, whereas the complicated forms have additional features (optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, epilepsy, ataxia, ichthyosis, mental retardation, and deafness). Three X-linked loci have been identified for the complicated HSP, while mutations in the proteolipid gene (PLP) (locus SPG2) were implicated in both pure and complicated forms. The absence of identified mutations in the PLP gene in families with both complicated and pure HSP, linked to the SPG2 locus, suggests the existence of another gene in close proximity. We had previously reported a large pedigree with an X-linked form of pure HSP affecting 24 males [Zatz et al., 1976: J Med Genet 13:217-222]. Here, we present the results of linkage analysis in 19 members of this Brazilian family with markers in or near the PLP locus. Positive LOD scores were obtained with markers at the PLP locus (Zmax = 2.41 at Theta = 0); however, no mutation was found in the coding region of PLP, the intron-exon boundaries, or part of the promoter region. The possibility of a duplication of the PLP gene was also excluded. These results suggest either that there is another X-linked gene in close proximity to the PLP gene or that a novel mutation in the noncoding regions of the PLP gene may cause the disease in this family.