[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].

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.