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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association

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Author(s):
Souza, Manoel Carlos L. A. [1] ; Martins, Clarissa S. [1] ; Silva-Junior, Ivan M. [1] ; Chriguer, Rosangela S. [1] ; Bueno, Ana C. [2] ; Antonini, Sonir R. [2] ; Silva, Jr., Wilson Araujo [3, 4] ; Zago, Marco A. [1] ; Moreira, Ayrton C. [1] ; de Castro, Margaret [1]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo FMRP USP, Sch Med Ribeirao Preto, Dept Internal Med, Ribeirao Preto, SP - Brazil
[2] FMRP USP, Dept Pediat, Ribeirao Preto, SP - Brazil
[3] FMRP USP, Dept Genet, Ribeirao Preto, SP - Brazil
[4] FMRP USP, Ctr Med Genom, Ribeirao Preto, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Arquivos Brasileiros de Endocrinologia e Metabologia; v. 58, n. 1, p. 53-61, FEB 2014.
Web of Science Citations: 10
Abstract

Objective : The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. Materials and methods : We assessed NR3C1 polymorphisms in Brazilians of Caucasian, African and Asian ancestry (n = 380). In a subgroup (n = 40), we compared the genotypes to glucocorticoid (GC) sensitivity, which was previously evaluated by plasma (PF) and salivary (SF) cortisol after dexamethasone (DEX) suppression tests, GC receptor binding affinity (K d ), and DEX-50% inhibition (IC 50 ) of concanavalin-A-stimulated mononuclear cell proliferation. p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) allelic discrimination was performed by Real-Time PCR (Polymerase Chain Reaction). Exons 3 to 9 and exon/intron boundaries were amplified by PCR and sequenced. Results : Genotypic frequencies (%) were: rs6195 (n = 380; AA:96.6/AG:3.14/GG:0.26), rs6189-6190 (n = 264; GG:99.6/GA:0.4), rs41423247 (n = 264; CC:57.9/CG:34.1/GG:8.0), rs6188 (n = 155; GG:69.6/GT:25.7/TT:4.7), rs258751 (n = 150; CC:88.0/CT:10.7/TT:1.3), rs6196 (n = 176; TT:77.2/TC:20.4/CC:2.4), rs67300719 (n = 137; CC:99.3/CT:0.7), and rs72542757 (n = 137; CC:99.3/CG:0.7). The rs67300719 and rs72542757 were found only in Asian descendants, in whom p.N363S and p.ER22/23EK were absent. The p.ER22/23EK was observed exclusively in Caucasian descendants. Hardy-Weinberg equilibrium was observed, except in the Asian for rs6188 and rs258751, and in the African for p.N363S. The K d , IC 50 , baseline and after DEX PF or SF did not differ between genotype groups. However, the mean DEX dose that suppressed PF or SF differed among the BclI genotypes (P = 0.03). DEX dose was higher in GG- (0.7 ± 0.2 mg) compared to GC- (0.47 ± 0.2 mg) and CC-carriers (0.47 ± 0.1 mg). Conclusion : The genotypic frequencies of NR3C1 polymorphisms in Brazilians are similar to worldwide populations. Additionally, the BclI polymorphism was associated with altered pituitary-adrenal axis GC sensitivity. (AU)

FAPESP's process: 03/00327-8 - Integrative studies of the body fluid homeostasis: physiological and molecular aspects of the neuroendocrine control and clinical and experimental evaluation
Grantee:José Antunes Rodrigues
Support Opportunities: Research Projects - Thematic Grants