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Association of genes involved in nicotine and tobacco smoke toxicant metabolism (CHRNA3/5, CYP2A6, and NQO1) and DNA repair (XRCC1, XRCC3, XPC, and XPA) with chronic obstructive pulmonary disease

  • Genomics. Transcriptomics
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Abstract

Polymorphisms of the CHRNA5/A3, CYP2A6, NQO1, XPC, XRCC1, CRCC3, XPD, and XPA genes were tested for association with the development and progression of chronic obstructive pulmonary disease (COPD) in ethnic Tatars. CHRNA5 (rs16969968) (P = 0.0001, OR = 2.24) and CHRNA3 (rs1051730) (P = 0.0001, OR = 2.72) polymorphisms were associated with COPD development in the recessive model. The nondeletion variant of CYP2A6 (del) was associated with COPD risk (P = 0.00001, OR = 2.77). NQO1 (rs113341), XRCC1 (rs25487), XRCC3 (rs86539), XPC (rs2228001), and XPA (rs1800975) were associated with COPD in the additive model (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, respectively). A gene-by-environment interaction was observed for XPA (rs1800975) and the smoking status (P interact = 0.002), and the rs16969968 and rs1051730 polymorphisms of the CHRNA3/5 gene cluster showed an association with COPD only in smokers. Carriers of the CYP2A6 deletion (CYP2A6*4) had a lower smoking index (P = 0.0019). XRCC3 (rs861539) genotype TT was characterized by lower indices of pulmonary function, including vital capacity (VC) (P = 0.0487), forced vital capacity (FVC) (P = 0.0032), and forced expiratory volume in 1 second (FEV1) (P = 0.02). FVC was found to depend on the genotype at XPA (rs1800975) (P = 0.0028).

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Abbreviations

GWAS:

genome-wide association study

MAF:

minor allele frequency

GOLD:

Global Initiative for Chronic Obstructive Lung Disease

NQO1:

NAD(P)H-quinone oxidoreductase 1

COPD:

chronic obstructive pulmonary disease

VC:

vital capacity

FVC:

forced vital capacity

ROS:

reactive oxygen species

FEV1:

forced expiratory volume in 1 second

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, 450054, Russia

    G. F. Korytina, L. Z. Akhmadishina, O. V. Kochetova & T. V. Victorova

  2. Bashkortostan State Medical University, Ufa, 45000, Russia

    Yu. V. Burduk, Yu. G. Aznabaeva, Sh. Z. Zagidullin & T. V. Victorova

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  1. G. F. Korytina
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  2. L. Z. Akhmadishina
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  3. O. V. Kochetova
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Correspondence to G. F. Korytina.

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Original Russian Text © G.F. Korytina, L.Z. Akhmadishina, O.V. Kochetova, Yu.V. Burduk, Yu.G. Aznabaeva, Sh.Z. Zagidullin, T.V. Victorova, 2014, published in Molekulyarnaya Biologiya, 2014, Vol. 48, No. 6, pp. 939–951.

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Korytina, G.F., Akhmadishina, L.Z., Kochetova, O.V. et al. Association of genes involved in nicotine and tobacco smoke toxicant metabolism (CHRNA3/5, CYP2A6, and NQO1) and DNA repair (XRCC1, XRCC3, XPC, and XPA) with chronic obstructive pulmonary disease. Mol Biol 48, 823–834 (2014). https://doi.org/10.1134/S0026893314060090

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