Association of Polymorphisms of Xenobiotic-Metabolizing Genes with Glucocorticoid-Induced Osteoporosis in Patients with Bronchial Asthma

作者：Gra O A^*; Moskalenko M V; Filimonova N A; Baranova I A; Glotov A S; Surzhikov S A; Koroleva O V; Goldenkova Pavlova I V; Nasedkina T V

来源：Molecular Biology, 2012, 46(1): 94-101.

DOI：10.1134/S0026893312010098

• bronchial asthma
• osteoporosis
• polymorphism
• xenobiotic-metabolizing genes
• predisposition
• biochip

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. DOI: 10.1134/S0026893312010098

• 出版日期2012-2