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Genetic make up and external stimuli interact to cause lung disease

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A prospective epidemiological study in coal miners is the first to suggest that genetic background and environmental oxidative stimuli interact to influence development of pneumoconiosis.

Tumour necrosis factor α (TNF) −308 genotype affected glutathione peroxidase (GSH-Px) and catalase activities in red blood cells. Genotypes with homozygous 22, heterozygous 12 alleles significantly reduced GSH-Px activity and increased catalase activity. Lymphotoxin α (LTA) NcoI genotype seemed to have no effect.

TNF−308 genotype and exposure to environmental oxidants together influenced GSH-Px activity under oxidative stress with cumulative occupational dust exposure but not with cigarette smoking. TNF−308 22, 12 genotypes had significantly reduced GSH-Px activity with high dust exposure (>71 mg/m3/year) and 2.5 times higher five year incidence of pneumoconiosis than with low exposure. LTA NcoI genotype interacted with catalase activity on the incidence of pneumoconiosis. Low catalase activity (⩽107 k/g Hb) and LTA NcoI 22 genotype resulted in significantly higher disease incidence than high catalase activity and 11, 12 genotypes.

There was no direct relation between TNF−308 genotypes and cumulative dust exposure or disease incidence, but a borderline relation for LTA NcoI 11, 12 genotypes and significant relation between genotype 22 and disease severity. Age, BMI, smoking, and current exposure to coal dust were unrelated to genotypes 11, 12, 22 of both genes.

Genetic differences may underlie conflicting reports about individuals’ responses to environmental oxidants. This study tested the hypothesis that gene polymorphisms in two prominent proinflammatory molecules in lung disease influence oxidative responses in 253 coal miners variously exposed to cigarette smoke and coal dust.

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