Polymorphisms of the <i>GR</i> and <i>HSD11B1</i> genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease

Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Kàroly; Patócs, Attila

doi:10.1111/cen.13022

Cited by 15 publications

(9 citation statements)

References 43 publications

(82 reference statements)

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“…On the other hand, our previous analysis conducted in patients with primary adrenal failure who require lifelong glucocorticoid substitution, revealed that HSD11B1 rs3753519 was associated with BMI and fasting plasma glucose, whereas rs12086634 appeared associated with circulating cholesterol [38]. Analogous findings with regard to rs4844880, BMI and weight gain during glucocorticoid replacement were reported in a smaller Hungarian cohort of subjects with adrenocortical insufficiency [39]. These patients are usually treated with hydrocortisone, identical with the natural cortisol molecule, but its proper dosage, mimicking natural diurnal rhythm of cortisol secretion, remains a challenging issue.…”

Section: Discussionmentioning

confidence: 52%

Lack of association of the HSD11B1 gene polymorphisms with obesity and other traits of metabolic syndrome in children and adolescents

Fichna

Krzyśko-Pieczka²,

Żurawek

et al. 2017

Clinical Diabetology

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Section: Discussionmentioning

confidence: 52%

Lack of association of the HSD11B1 gene polymorphisms with obesity and other traits of metabolic syndrome in children and adolescents

Fichna

Krzyśko-Pieczka²,

Żurawek

et al. 2017

Clinical Diabetology

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“…Thirty-one GR loss-of-function mutations have been associated with a glucocorticoid resistance syndrome (MIM#615962) (13,23,24,25), while 33 index cases have been reported (13,23,24). These mutations are summarized in Table 1 and depicted in Fig.…”

Section: Nr3c1 Mutationsmentioning

confidence: 99%

GENETICS IN ENDOCRINOLOGY: Glucocorticoid resistance syndrome

Vitellius

Lombès

2020

European Journal of Endocrinology

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Glucocorticoids (GC) such as cortisol regulate multiple physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene in humans). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, and recruitment of functional transcriptional machinery. Generalized glucocorticoid resistance syndrome, due to GR loss-of-function mutations, may be related to the impairment of one of the GC signaling steps. To date, 31 NR3C1 loss-of-function mutations have been reported in patients presenting with various clinical signs such as hypertension, adrenal hyperplasia, hirsutism or metabolic disorders associated with biological hypercortisolism but without Cushing syndrome signs and no negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Functional characterization of GR loss-of-function mutations often demonstrates GR haploinsufficiency and a decrease of GR target gene induction in relevant cell types. The main signs at presentation are very variable from resistant hypertension, bilateral adrenal hyperplasia likely related to increased ACTH levels but not exclusively, hirsutism to isolated renin-angiotensin-aldosterone system abnormalities in a context of 11βHSD2 deficiency. Some mutated GR patients are obese or overweight together with a healthier metabolic profile that remains to be further explored in future studies. Deciphering the molecular mechanisms altered by GR mutations should enhance our knowledge on GR signaling and ultimately facilitate management of GC-resistant patients. This review also focuses on the criteria facilitating identification of novel NR3C1 mutations in selected patients.

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“…Genotyping of the BclI, N363S, and A3669G polymorphisms was performed in peripheral blood DNA isolated with commercially available DNA Isolation Kit (QIAamp DNA Blood Mini Kit (QiampDNA Blood Kit, Qiagen, USA). Genotypes for the BclI and the N363S variants were determined by allelespecific polymerase chain reaction (PCR) as earlier reported [11][12][13]. Genotypes for the A3669G polymorphism were analysed using a primer-probe set purchased as predesigned Taqman allelic discrimination assay according to the manufacturer's instructions (Applied Biosystems, Applied Biosystems Group 850 Lincoln Center Drive Foster City, CA) on a 7500 Fast Real-Time PCR System (Applied Biosystems).…”

Section: Dna Extraction and Genotyping Of Gr Gene Polymorphismsmentioning

confidence: 99%

Polymorphisms of human glucocorticoid receptor gene in systemic lupus erythematosus: a single-centre result

et al. 2019

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Background SLE is a systemic autoimmune disorder with multiple organ manifestations. Despite of the innovations glucocorticoids (GC) have still remained the first-line therapy in SLE. Besides HSD11B enzymes, intracellular glucocorticoid receptors (GR) affect tissue-specific cortisol effect and the consequent signalisation pathway. SNPs of the glucocorticoid receptor gene (NR3C1) modulate individual sensitivity to glucocorticoids. Our aim was to determine the allele frequency of the three, clinically most important SNPs in a SLE patient population in comparison to healthy volunteers and to find association with particular manifestations of SLE. Methods We analysed results of 104 SLE patients compared to 160 healthy subjects. All patients were genotyped for the functional GR polymorphisms BclI, N363S, and A3669G. The GR gene polymorphisms were determined using allele-specific PCR and Taqman allelic discrimination assays. Results The BclI allele frequency was lower in the SLE group compared to the healthy control group. The central nervous system and especially psychiatric symptoms developed more frequently in the BclI carriers compared to none carriers. The prevalence of theA3669G polymorphism was the same in both groups, but showed a negative association with the psychiatric symptoms. Conclusion The increased and decreased sensitivity associated with GR BclI and A3669G polymorphisms could have a pathogenic significance in SLE especial with the central nervous system and psychiatric symptoms. Improving our knowledge on the importance of GR polymorphisms may reveal their pathophysiologic and therapeutic consequences.

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Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease

Abstract: The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients.

Cited by 15 publications

References 43 publications

Lack of association of the HSD11B1 gene polymorphisms with obesity and other traits of metabolic syndrome in children and adolescents

Lack of association of the HSD11B1 gene polymorphisms with obesity and other traits of metabolic syndrome in children and adolescents

GENETICS IN ENDOCRINOLOGY: Glucocorticoid resistance syndrome

Polymorphisms of human glucocorticoid receptor gene in systemic lupus erythematosus: a single-centre result

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