NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association / Polimorfismos NR3C1 em brasileiros de ascendência caucasiana, africana e asiática: sensibilidade aos glicocorticoides e associação de genótipos
Souza, Manoel Carlos L. A.; Martins, Clarissa S.; Silva Junior, Ivan M.; Chriguer, Rosangela S.; Bueno, Ana C.; Antonini, Sonir R.; Silva Jr., Wilson Araújo; Zago, Marco A.; Moreira, Ayrton C.; Castro, Margaret de.
Arq. bras. endocrinol. metab
; 58(1): 53-61, 02/2014. tab, graf
Artículo
en Inglés
| LILACS | ID: lil-705239
Objective:
The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. Materials andmethods:
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; AA96.6/AG3.14/GG0.26), rs6189-6190 (n = 264; GG99.6/GA0.4), rs41423247 (n = 264; CC57.9/CG34.1/GG8.0), rs6188 (n = 155; GG69.6/GT25.7/TT4.7), rs258751 (n = 150; CC88.0/CT10.7/TT1.3), rs6196 (n = 176; TT77.2/TC20.4/CC2.4), rs67300719 (n = 137; CC99.3/CT0.7), and rs72542757 (n = 137; CC99.3/CG0.7). 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 ...
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