A 646C\u2009>\u2009G (rs41423247) polymorphism of the glucocorticoid receptor as a risk factor for hyperglycaemia diagnosed in pregnancy\u2014data from an observational study

Agnieszka Zawiejska,Jacek Brązert,Agnieszka Lewicka-Rabska,Anna Bogacz,Przemysław Mikołajczak,Rafał Iciek,Maciej Brązert

doi:10.1007/s00592-021-01799-3

Abstract

AimHyperglycaemia diagnosed in pregnancy (HiP) is a serious and frequent complication of pregnancy, increasing the risk for adverse maternal and neonatal outcomes. Investigate whether allelic variations of the glucocorticoid receptor are related to an increased risk of HiP.MethodThe following polymorphisms of the glucocorticoid receptor (GR) were investigated in the cohort study of N = 197 pregnant women with HiP and N = 133 normoglycemic pregnant controls: 646C > G (rs41423247), N363S (rs6195), ER23/22EK (rs6190, rs6189).ResultsA GG variant of the rs41423247 polymorphism was associated with a significantly higher risk for HiP: OR 1.94 (1.18; 3.18), p = 0.009. The relationship remained significant after controlling for maternal age and prepregnancy BMI: OR 3.09 (1.25; 7.64), p = 0.014.ConclusionsThe allelic GG variant of the 646C > G (rs41423247) polymorphism is associated with an increased risk for hyperglycaemia in pregnancy.

Highlights

Glucocorticoids and their receptor (GR) provide an essential pleiotropic regulatory system for mammalian metabolism
A total of 26.8% of these patients had early Hyperglycaemia diagnosed in pregnancy (HiP), meaning their disease was diagnosed before the 24th week of gestation
To the best of our knowledge, our study is the first cohort study reporting an association between a genetic variant in the glucocorticoid receptor associated with increased sen‐ sitivity to endogenous glucocorticoids and an elevated risk for hyperglycaemia diagnosed in pregnancy

Summary

Introduction

Glucocorticoids and their receptor (GR) provide an essential pleiotropic regulatory system for mammalian metabolism. Available evidence describes an association between GR gene variants and altered response to glucocorticoids in the target tissues due to the altered transcriptional activity of the GR [1]. According to the studies by Russcher [2], car‐ riers of the ER22/23EK and 3669A > G variant presented a reduced transcriptional activity of the GR, which might translate into a reduced risk of T2DM and cardiovascular disorders as a result of a relative insensitivity to endogenous glucocorticosteroids [1]. Studies on the other variants of the receptor, Bcl I and N363S, linked these variants to increased sensitivity to endogenous glucocorticosteroids [1]. Stud‐ ies performed in cohorts from the UK and the Netherlands translated these genetic findings into metabolically less favourable phenotypes of increased BMI or increased WHR in the adult carriers of the N363S polymorphism [3, 4]

Objectives

Methods

Results

Conclusion