Endocrine Abstracts

Objective: Previous studies indicated that two glucocorticoid receptor gene polimorphisms bclI and N363S (GC-S) are associated with increased sensitivity to glucocorticoids and two other polymorphisms 9β and ER22/23EK (GC-I) are related to decreased sensitivity to glucocorticoids. The aim of the study was to determine whether these genetic changes can effect on the occurence of steroid-induced adverse events.

Methods: One hundred and fifty patients treated with glucocorticoids for over 3 months due to connective-tissue disease underwent clinical and biochemical evaluation. Genotyping of polymorphisms was carried out using a high resolution post PCR method that analyzes High Resolution Melting profiles. Analysis was performed comparing adverse effects of GCS treatment in carriers of GC-S or GC-I polymorphisms vs noncarriers.

Results: There was no significant difference in age, time of treatment, current and cumulative dose of glucocorticoids, BMI, waist circumference, bone mineral density, lean and fat mass, HOMA-IR, HbA1c, Matsuda Index, lipid profile, insulin or glucose concentration in OGTT or presence of adverse events of glucocorticoid treatment, including arterial hypertension, CVD, diabetes, osteopenia/osteoporosis and ‘Cushingoid appearence’ between GC-S carriers (n=74) vs noncarriers (n=76). GC-I carriers (n=46) had higher median cumulative dose of treatment (18.4 g vs 11.8 g, P=0.03) and there was higher prevalence of osteopenia/osteoporosis in this group comparing to GC-I noncarriers (n=104). There was no significance in other analyzed parameters.

Conclusions: The results of the present study show that there is no impact of glucocorticoid receptor polymorphisms on occurrence of steroid-induced adverse effects. Higher prevalence of osteopenia/osteoporosis in GC-I carriers is probably related to higher cumulative dose of glucocorticoids.