EXPRESSION OF OXIDATIVE STRESS AND INFLAMMATION-RELATED GENES (GSTM1, GSTT1, TNF-Α) ASSOCIATED WITH AIR POLLUTION (PM2.5, PM10) AMONG THE POPULATIONS OF MAJOR CITIES IN UZBEKISTAN (TASHKENT, NUKUS, SAMARKAND)

Abstract

Background: Air pollution, particularly particulate matter (PM2.5 and PM10), poses a significant public health threat in urban centers of Central Asia. Uzbekistan's major cities—Tashkent, Nukus, and Samarkand—experience elevated PM concentrations from industrial activities, vehicular emissions, and natural sources such as sand and dust storms. Genetic susceptibility to pollution-induced health effects is mediated through variations in genes regulating oxidative stress and inflammatory responses.

Objective: This study investigated the expression patterns of oxidative stress-related genes (GSTM1, GSTT1) and the pro-inflammatory cytokine gene (TNF-α) in relation to ambient PM2.5 and PM10 exposure levels among populations residing in Tashkent, Nukus, and Samarkand, Uzbekistan.

Methods: A cross-sectional study was conducted involving 450 participants (150 per city). Air quality monitoring for PM2.5 and PM10 was performed using fixed monitoring stations over 12 months. Gene expression analysis was conducted via quantitative real-time PCR (qRT-PCR) on peripheral blood leukocytes. Statistical analyses included ANOVA, Pearson correlation, and multiple linear regression to assess associations between PM exposure and gene expression levels.

Results: Annual mean PM2.5 concentrations were highest in Tashkent (42.3 ± 8.7 µg/m³), followed by Nukus (38.5 ± 9.2 µg/m³) and Samarkand (28.7 ± 6.4 µg/m³), all exceeding WHO guidelines. PM10 levels showed similar patterns. GSTM1 expression was significantly downregulated in Tashkent (2.1-fold, p<0.001) and Nukus (1.8-fold, p<0.01) compared to Samarkand. GSTT1 expression showed a 1.6-fold reduction in Tashkent (p<0.01). TNF-α expression was significantly upregulated in Tashkent (3.4-fold, p<0.001) and Nukus (2.7-fold, p<0.001). Strong positive correlations were observed between PM2.5 exposure and TNF-α expression (r=0.72, p<0.001), while negative correlations existed between PM levels and GSTM1/GSTT1 expression.

Conclusion: Elevated PM exposure in Uzbekistan's major cities is associated with significant alterations in oxidative stress and inflammation-related gene expression. The downregulation of detoxifying enzymes (GSTM1, GSTT1) coupled with upregulation of the pro-inflammatory TNF-α gene suggests a molecular mechanism linking air pollution to increased health risks, with implications for precision public health interventions.