Glucocorticoid receptor Gene (NR3C1) Polymorphisms and Haplotypes in patients with congenital adrenal hyperplasia
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Universidade Federal de Minas Gerais
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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.
Abstract
Assunto
Hiperplasia Suprarrenal Congênita, Receptores de Glucocorticoides, Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares, Polimorfismo Genético, Haplótipos
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Congenital adrenal hyperplasia, genetic polymorphisms, glucocorticoid receptor gene, haplotypes, nuclear receptor subfamily 3 group C member 1
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https://www.sciencedirect.com/science/article/pii/S0303720721002434?via%3Dihub