Association of polymorphisms of xenobiotic-metabolizing genes with glucocorticoid-induced osteoporosis in patients with bronchial asthma

Abstract

Investigation of risk factors for glucocorticoid-induced (GI) osteoporosis, which is one of the most frequent and serious complications of long-term systemic glucocorticoid (SGC) therapy for bronchial asthma, is a topical issue of preventative medicine. In the present work, allele-specific hybridization on a biochip was used to determine the allele and genotype frequencies of eight candidate genes for GI osteoporosis in 137 patients with bronchial asthma receiving long-term SGC therapy. The MTHFR polymorphism 677C>T showed a significant association with the proximal femur mineral density (Z-score) in patients treated with SGC (nonparametric Kruskal-Wallis ANOVA, p = 0.0013). On the other hand, carriers of the null genotype by the GSTM1 insertion-deletion polymorphism had lower bone mineral density Z-scores than carriers of at least one functional GSTM1 allele (Mann-Whitney U-test with the Bonferroni correction, p = 0.034). Analysis of gene-gene interactions showed that the MTHFR 677C/C/GSTM1 null genotype combination was associated with significantly lower bone mineral density Z-scores than other genotype variants (Kruskal-Wallis ANOVA, p = 0.0012). Thus, the MTHFR and GSTM1 alleles can modulate the risk of GI osteoporosis in patients with bronchial asthma, which is very important for the identification of patients at a high risk of osteoporosis among individuals receiving SGC, as well as inhaled glucocorticoids.