Endocrine Abstracts (2006) 11 P8

Is there any combined influence of the N363S polymorphism in the glucocorticoid receptor gene and the BsmI polymorphism in the vitamin D receptor gene on the occurrence of glucocorticoid-induced osteoporosis in patients with bronchial asthma?

U Tworowska1, B Bidzinska-Speichert1, A Obojski2, M Demissie1, JW Koper3 & R Slezak4

1Dept. of Endocrinology, Daibetology and Isotope Treatment, Medical University of Wroclaw, Wroclaw, Poland; 2Dept. of Internal Medicine and Allergology, Medical University of Wroclaw, Wroclaw, Poland; 3Dept. of Internal Medicine, Erasmus MC, Rotterdam, Netherlands; 4Dept. of Genetics, Medical University of Wroclaw, Wroclaw, Poland.

Osteoporosis has a strong genetic component and is a common side-effect in patients with long-term glucocorticoid (GC) treatment. Vitamin D plays an important role in bone metabolism, and polymorphisms in its receptor (VDR) gene have been implicated in the pathogenesis of osteoporosis. On the other hand, variability in the sensitivity to GCs, due to polymorphic variants of the glucocorticoid receptor (GR) gene was observed in patients treated with GCs, both with regard to the efficacy of treatment and to the prevalence of side effects. The aim of the study was to analyze the combined influence of polymorphisms in the VDR and GR genes in determining the susceptibility to osteopororosis. Materials and methods: the following groups were studied: 1. asthmatic patients, divided into the subgroups: SS – patients treated with systemic GC (n=38, 27 women), IS – patients treated with inhaled GC (n=34, 29 women), NS – patients treated with other drugs than GC –(n=13, 9 women), 2. controls, healthy volunteers (n=31, 17 women). BMD was measured using the DXA method. Serum osteocalcin and ICTP were measured using IRMA and RIA methods respectively. GR gene genotypes were determined using custom designed Allelic Discrimination Assays and VDR genotypes were determined by PCR followed by enzymatic digestion of the products using the BsmI restriction enzyme. Results: Although heterozygotic carriers of the 363S allele showed a tendency towards a lower BMD in the lumbar spine, neither the GR N363S, nor VDR BsmI restriction fragment length polymorphism was associated with BMD or any of the bone-related serum measurements. We identified no significant gene-to-gene interaction effect for the VDR locus and GR N363S polymorphisms, which could impact BMD levels. Conclusions: Neither of these polymorphisms separately, nor their co-occurrence seems to be a marker of glucocorticoid–induced osteoporosis risk, however this should be verified in a larger, population–based study.

The study protocol was approved by Ethical Committee of Wroclaw Medical University.