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In addition, p.N363S (rs6195), p.ER22\/23EK (rs6189\u20106190), and <jats:italic>BclI<\/jats:italic> (rs41423247) SNPs were evaluated by quantitative polymerase chain reaction allelic discrimination. Exons 3 to 9 and exon\/intron boundaries of <jats:italic>NR3C1<\/jats:italic> were sequenced. GR isoforms and cytokines (<jats:italic>IL1B<\/jats:italic>, <jats:italic>IL2, IL4<\/jats:italic>, <jats:italic>IL6<\/jats:italic>, <jats:italic>IL8<\/jats:italic>, <jats:italic>IL10, IFN\u03b3<\/jats:italic>, <jats:italic>TNF\u03b1<\/jats:italic>) expression were assessed by quantitative polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma and salivary cortisol (nmol\/L) after 1\u2010mg DEX were higher in MetS patients compared with controls (PF: 70.2\u00a0\u00b1\u00a017.3 vs 37.9\u00a0\u00b1\u00a02.6, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.02, and SF: 4.9\u00a0\u00b1\u00a01.7 vs 2.2\u00a0\u00b1\u00a00.3, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001). After all DEX doses, a lower number of MetS patients suppressed plasma and salivary cortisol compared with controls. The <jats:italic>BclI<\/jats:italic> genotypic frequencies (%) differed between patients (CC:56\/CG:44) and controls (CC:50\/CG:32.5\/GG:17.5) (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.03). The <jats:italic>GR\u03b2<\/jats:italic> was overexpressed (fold\u00a0=\u00a0100.0; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.002) and IL4 (fold\u00a0=\u00a0\u2212265.0; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001) was underexpressed in MetS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MetS patients exhibited decreased HPA sensitivity to glucocorticoid feedback. Moreover, the <jats:italic>BclI<\/jats:italic> polymorphism lower frequency, <jats:italic>GR\u03b2<\/jats:italic> overexpression, and IL4 underexpression might underlie the molecular mechanism of glucocorticoid resistance in MetS. Thus, HPA axis dysregulation might contribute to MetS pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.2842","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T02:16:41Z","timestamp":1470795401000},"source":"Crossref","is-referenced-by-count":37,"title":["HPA axis dysregulation, <i>NR3C1<\/i> polymorphisms and glucocorticoid receptor isoforms imbalance in metabolic syndrome"],"prefix":"10.1002","volume":"33","author":[{"given":"Clarissa Silva","family":"Martins","sequence":"first","affiliation":[{"name":"Department of Internal Medicine \u2010 Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine \u2010 Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  S\u00e3o Paulo 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