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Type:	Artigo de Periódico
Title:	Glucocorticoid receptor Gene (NR3C1) Polymorphisms and Haplotypes in patients with congenital adrenal hyperplasia
Authors:	Thais Ramos Villela Cristina Botelho Barra André Rolim Belisário Marcelo Rizzatti Luizon Ana Cristina Simões e Silva Ivani Novato Silva
Abstract:	Background: Lifelong glucocorticoid (GC) replacement is the mainstay treatment of congenital adrenal hyper plasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD). Challenges posed by therapeutic management of these patients are well known, but novel insights into the variability in clinical response to GC highlight a role for single nucleotide polymorphisms (SNPs) of the glucocorticoid receptor gene (NR3C1). Aim: To assess whether six commonly studied NR3C1 SNPs, which were previously associated with modified response to GC, are associated with CAH. We further assessed the linkage disequilibrium (LD) among these NR3C1 SNPs and their combination into haplotypes. Methods: Genotypes were determined by Taqman allele discrimination assays for Tth111I (rs10052957), ER22 (rs6189), 23 EK (rs6190), N363S (rs56149945), BclI (rs41423247) and 9β (rs6198) in a Brazilian cohort of 102 unrelated 21-OHD patients and 163 unrelated healthy subjects (controls). Haplotypes were estimated using Haplo.stats, and LD among SNPs using Haploview. Results: Heterozygous subjects for Tth111I were more frequent in 21-OHD patients (P = 0.004), while hetero zygous for BclI were more frequent in controls (P = 0.049). We found a strong LD among the six NR3C1 SNPs, and four out of six common haplotypes contained the Tth111I-variant. Although we found no significant dif ferences in overall haplotype analysis, the BclI-haplotype was less frequent among 21-OHD patients (P = 0.0180). Conclusions: BclI-haplotype was less common and heterozygous for Tth111I were more frequent in 21-OHD pa tients, while heterozygous for BclI were more frequent in controls. Our novel findings may contribute to further clinical studies on the prognostic value of NR3C1 haplotypes towards individualized treatment for 21-OHD patients.
Subject:	Hiperplasia Suprarrenal Congênita Receptores de Glucocorticoides Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares Polimorfismo Genético Haplótipos
language:	eng
metadata.dc.publisher.country:	Brasil
Publisher:	Universidade Federal de Minas Gerais
Publisher Initials:	UFMG
metadata.dc.publisher.department:	MED - DEPARTAMENTO DE PEDIATRIA
Rights:	Acesso Restrito
metadata.dc.identifier.doi:	https://doi.org/10.1016/j.mce.2021.111399
URI:	http://hdl.handle.net/1843/57629
Issue Date:	21-Jul-2017
metadata.dc.url.externa:	https://www.sciencedirect.com/science/article/pii/S0303720721002434?via%3Dihub
metadata.dc.relation.ispartof:	Molecular and Cellular Endocrinology
Appears in Collections:	Artigo de Periódico

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