[Polymorphisms in xenobiotic-metabolizing genes in the pathogenesis of glucocorticoid-induced osteoporosis in patients with bronchial asthma].
Search for and study of risk factors for glucocorticoid-induced (GI) osteoporosis, as one of the most frequent and serious complications of long-term systemic glucocorticoid (SGC) therapy for bronchial asthma are an important problem of prevention medicine. In the present work to determine the frequencies of genotypes and alleles of eight candidate genes of GI osteoporosis in 137 patients with bronchial asthma receiving long-term SGC therapy, using allele-specific hybridization on the biochip. In the analysis of gene polymorphism MTHFR 677C>T showed a statistically significant association between genotypes for this gene and proximal femur mineral density (BMD) for the Z-criterion in patients treated with SGC (non-parametric ANOVA Kruskal-Wallis p = 0.0013). In addition, the analysis of insertion-deletion polymorphism of GSTM1 found that carriers of GSTM1 "null" genotype have lower values of BMD Z-criterion, than carriers of at least one functional allele of GSTM1 gene (Mann-Whitney U-test with Bonferroni correction, p = 0.034). Analysis of gene-gene interactions revealed that carriers of MTHFR genotype 677C/C in combination with GSTM1 "null" genotype characterized by a statistically significant lower values of BMD Z-criterion, than carriers of other variants of genotypes (ANOVA Kruskal-Wallis, p = 0.0012). Thus, the alleles of MTHFR and GSTM1 genes may modulate the risk of GI osteoporosis in patients with bronchial asthma, which is very important to identify group of patients with high risk for osteoporosis among individuals receiving SGC as well as inhaled glucocorticoids.
D000328:Adult; D000483:Alleles; D001249:Asthma / Q000188:drug therapy*; D015519:Bone Density / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
D005938:Glucocorticoids; D005982:Glutathione Transferase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)