1. [Association of the nicotine and cigarette smoke toxicants metabolic (CHRNA3/5, CYP2A6, NQO1) and DNA repair genes (XRCC1, XRCC3, XPC, XPA) with chronic obstructive pulmonary disease].
- Author
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Korytina GF, Akhmadishina LZ, Kochetova OV, Burdiuk IuV, Aznabaeva IuG, Zagidullin ShZ, and Victorova TV
- Subjects
- Aged, Alleles, Biomarkers metabolism, Case-Control Studies, Cytochrome P-450 CYP2A6 genetics, Female, Gene Expression, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Models, Genetic, Nicotine toxicity, Polymorphism, Genetic, Pulmonary Disease, Chronic Obstructive etiology, Pulmonary Disease, Chronic Obstructive pathology, Receptors, Nicotinic genetics, Respiratory Function Tests, Smoking adverse effects, X-ray Repair Cross Complementing Protein 1, DNA-Binding Proteins genetics, NAD(P)H Dehydrogenase (Quinone) genetics, Pulmonary Disease, Chronic Obstructive genetics, Xeroderma Pigmentosum Group A Protein genetics
- Abstract
The contribution of the polymorphic markers of the CHRNA5/A3, CYP2A6, NQO1, XPC, XRCC1, XRCC3, XPD, XPA genes to chronic obstructive pulmonary disease has been assessed. For this purpose, analysis of the gene polymorphisms in case/control groups in Tatar population has been performed. The CHRNA5 (rs16969968) (P = 0.0001, OR = 2.24), CHRNA3 (rs1051730) (P = 0.0001, OR = 2.72) were associated with significantly high risk of chronic obstructive pulmonary disease in recessive model. The disease risk was higher in homozygous carriers of normal allele of CYP2A6 (del) (P = 0.00001, OR = 2.77). Analysis showed an association of the NQO1 (rs1131341), XRCC1 (rs25487), XRCC3 (rs861539), XPC (rs2228001) and XPA (rs1800975) (P = 0.000001, OR = 2.67; P = 0.00001, OR = 0.51; P = 0.0003, OR = 1.76; P = 0.0004, OR = 0.54 and P = 0.007, OR = 0.74) in additive model with chronic obstructive pulmonary disease. We found a significant gene-by-environment interaction of smoking status and XPA (rs1800975) (Pinteract = 0.002); rs16969968, rs1051730 of CHRNA3/5 genes were significantly associated with chronic obstructive pulmonary disease only in smokers. The relationship between the CYP2A6(CYP2A6*4) and smoking pack-years was found (P = 0.0019). The TT genotype of XRCC3 (rs861539) were associated with decreased of lung function parameters: vital capacity % (P = 0.0487), forced vital capacity (%) (P = 0.0032) and forced expiratory volume in 1 s (%) (P = 0.02). The relationship between the XPA (rs1800975) and forced expiratory volume in 1 s (%) (P = 0.0028) was found.
- Published
- 2014