Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil

Xenobiotics can trigger degranulation of eosinophils and mast cells. In this process, the cells release several substances leading to bronchial hyperactivity, the main feature of atopic asthma (AA). GSTM1 and GSTT1 genes encode enzymes involved in the inactivation of these compounds. Both genes are polymorphic in humans and have a null variant genotype in which both the gene and corresponding enzyme are absent. An increased risk for disease in individuals with the null GST genotypes is therefore, but this issue is controversial. The aim of this study was to investigate the influence of the GSTM1 and GSTT1 genotypes on the occurrence of AA, as well as on its clinical manifestations. Genomic DNA from 86 patients and 258 controls was analyzed by polymerase chain reaction. The frequency of the GSTM1 null genotype in patients was higher than that found in controls (60.5% versus 40.3%, p = 0.002). In individuals with the GSTM1 null genotype the risk of manifested AA was 2.3-fold higher (95%CI: 1.4-3.7) than for others. In contrast, similar frequencies of GSTT1 null and combined GSTM1 plus GSTT1 null genotypes were seen in both groups. No differences in genotype frequencies were perceived in patients stratified by age, gender, ethnic origin, and severity of the disease. These results suggest that the inherited absence of the GSTM1 metabolic pathway may alter the risk of AA in southeastern Brazilian children, although this must be confirmed by further studies with a larger cohort of patients and age-matched controls from the distinct regions of the country

Homozygous deletion of the UGT2B17 gene is not associated with osteoporosis risk in elderly Caucasian women

SUMMARY: Previously, homozygous deletion of the UGT2B17 gene has shown association with hip fracture. Using a high-throughput qRT-PCR assay, we genotyped UGT2B17 copy number variation (CNV) in 1,347 elderly Caucasian women and examined for effects on bone phenotypes. We found no evidence of association between UGT2B17 CNV and osteoporosis risk in this population. INTRODUCTION: Genetic studies of osteoporosis commonly examine SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called CNV, also comprise a large amount of the genetic variability between individuals. Previously, homozygous deletion of the UGT2B17 gene in CNV 4q13.2, which encodes an enzyme that mediates the glucuronidation of steroid hormones, has shown association with the risk of hip fracture. METHODS: We used a quantitative real-time PCR assay for genotyping the UGT2B17 CNV in a well-characterized population study of 1,347 Caucasian women aged 75.2 ± 2.7 (mean ± SD) years, to assess the effect of the CNV on bone mass density (BMD) at the total hip site and osteoporosis risk. RESULTS: The UGT2B17 CNV distribution was consistent with the expected Hardy-Weinberg distribution and not different from frequencies previously reported in a Caucasian population. Data from ANCOVA of age- and weight-adjusted BMD for UGT2B17 CNV genotype showed no significant difference between genotype groups. Individuals with homozygous or heterozygous deletion of the UGT2B17 gene showed no increased risk of incident fragility fracture. CONCLUSIONS: These data suggest that quantitative real-time PCR is a rapid and efficient technique for determination of candidate CNVs, including the UGT2B17 CNV; however, we found no evidence of an effect of UGT2B17 CNV on osteoporosis risk in elderly Caucasian women

Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis

Oxidative stress is one of the main risk factors for asthma development. Glutathione S-transferases play an important role in antioxidant defences and may influence asthma susceptibility. In particular, GSTM1 and GSTT1 positive/null genotypes and the GSTP1 Ile105 Val polymorphism have been analyzed in a number of genetic association studies, with conflicting outcomes. Two previous meta-analyses have attempted to clarify the associations between GST genes and asthma, but these studies have also showed contrasting results. Our aim was to perform a meta-analysis that included independent genetic association studies on GSTM1, GSTP1, and GSTT1, evaluating also the effect of potential confounding variables (i.e. ethnicity, population age, and urbanization). Systematic review and meta-analysis of the effects of GST genes on asthma were conducted. The meta-analyses were performed using a fixed or, where appropriate, random effects model. The meta-analysis of the GSTM1 (n = 35), GSTT1 (n = 31) and GSTP1 (n = 28) studies suggests that no significant associations with asthma susceptibility were observed for GSTM1 and GSTP1 gene polymorphisms, whereas a significant outcome was detected for the GSTT1 positive/null genotype (pooled OR = 1.33, 95 %CI = 1.10-1.60). However, high between-study heterogeneity was identified in all the general analyses (p heterogenetity < 0.05). The stratification analysis seems to explain the heterogeneity only in few cases. This picture is probably due to the interactive process of genetics and environment that characterizes disease pathogenesis. Further studies on interactions of GST genes with the potential oxidative stress sources and with other antioxidant genes are needed to explain the role of GST enzymes in asthma