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Glutathione S-Transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma and COPD among Isocyanate exposed population of Bhopal, India

Author Affiliations

  • 1Department of Research, Bhopal Memorial Hospital and Research Centre, Karond Bypass Road, Bhopal (MP), INDIA-462038
  • 2Department of Research, Bhopal Memorial Hospital and Research Centre, Karond Bypass Road, Bhopal (MP), INDIA-462038

Res. J. Recent Sci., Volume 1, Issue (ISC-2011), Pages 219-223, (2012)

Abstract

The release of methyl isocyanate (MIC) in Bhopal, India, caused the worst industrial accident in history. Isocyanates are the most common low molecular weight chemicals to cause asthma and Chronic Obstructive Pulmonary Disorder (COPD), whereas their metabolites may be conjugated with glutathione by glutathione S-transferases (GSTs). Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of hazardous agents. We examined whether polymorphisms in the GSTM1, GSTP1 and GSTT1 genes modify allergic responses to isocyanate exposure, thus increasing risks for the development of isocyanate related- pulmonary disorders in a cohort of Bhopal. We compared clinical data - including gender, age and smoking habits - between the 2 groups. The study population consisted of 54 methyl isocyanate exposed subjects. Genotyping the polymorphisms in the GSTT1 and GSTM1 genes was performed using the multiplex PCR. The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP. GSTP1 genotype was significantly associated with the increased risk of asthma and COPD (RR =1.66, 95%CI, 0.412-3.29 and RR=1.586 ; 95%CI, 0.75-3.33 respectively). Asthmatic had a higher prevalence of the GSTP1Ile105val allele than the COPD group (53.48% and 44.1%, respectively; p =0 .002). Also, the presence of the GSTP1 homozygote Val/Val was less common in subjects with asthma (39.53%) than in COPD group (62.79%). Polymorphisms within genes of the GST superfamily were associated with risk of asthma and COPD in Bhopal population. No differences in genotype frequencies were perceived in patients stratified by age and gender. GSTM1 and GSTT1 had almost no association. The results suggest, for the first time, that the polymorphic GSTs, especially GST(P1), play an important role in inception of ill effects related to exposure to methyl isocyanate. Although about half of the subjects with lower FEV1 had never smoked, smoking was the main risk factor for the decreased FEV1 in COPD and asthmatic subjects. Our series of studies identified GST variants as a potential susceptibility locus to asthma and to lower lung function in COPD, asthmatic subjects, which may support the contention that genetic determinants of lung function influence susceptibility to asthma.

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