| Full text | |
| 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 |