title: [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].
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.
authors.forename: G F
authors.initials: GF
authors.lastname: Korytina
authors.forename: L Z
authors.initials: LZ
authors.lastname: Akhmadishina
authors.forename: O V
authors.initials: OV
authors.lastname: Kochetova
authors.forename: Iu V
authors.initials: IuV
authors.lastname: Burdiuk
authors.forename: Iu G
authors.initials: IuG
authors.lastname: Aznabaeva
authors.forename: Sh Z
authors.initials: ShZ
authors.lastname: Zagidullin
authors.forename: T V
authors.initials: TV
authors.lastname: Victorova
mesh_terms: D000368:Aged; D000483:Alleles; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009538:Nicotine / Q000633:toxicity; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011978:Receptors, Nicotinic / Q000235:genetics; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects; D000076105:X-ray Repair Cross Complementing Protein 1; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics*
chemical_list: D015415:Biomarkers; D065637:Cytochrome P-450 CYP2A6; D004268:DNA-Binding Proteins; D016660:NAD(P)H Dehydrogenase (Quinone); D009538:Nicotine; D011978:Receptors, Nicotinic; D000076105:X-ray Repair Cross Complementing Protein 1; D051760:Xeroderma Pigmentosum Group A Protein; C110901:X-ray repair cross complementing protein 3; C497314:XPA protein, human; C000619371:XRCC1 protein, human; C086984:XPC protein, human; C585710:CYP2A6 protein, human; C447479:NQO1 protein, human