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Polymorphic variants of glutamate receptor (GRIK5, GRIN2B) and serotonin receptor (HTR2A) genes are associated with chronic

  • Genomics. Transcriptomics
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Abstract

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system that affects primarily distal respiratory pathways and lung parenchyma. Smoking tobacco is a major risk factor for COPD. The relationship of HTR4 (rs3995090), HTR2A (rs6313), GRIK5 (rs8099939), GRIN2B (rs2268132), and CHRNB4 (rs1948) gene polymorphisms and COPD, as well as the contribution of these polymorphisms to the variations in quantitative characteristics that describe respiratory function, smoking behavior, and nicotine dependence was assessed in an ethnically homogeneous Tatar population. The polymorphisms of HTR2A (rs6313) (P = 0.026, OR = 1.42 for the CC genotype) and GRIN2B (rs2268132) (P = 0.0001, OR = 2.39 for the TT genotype) were significantly associated with increased risk of COPD. The AA genotype of GRIK5 (rs8099939) had a protective effect (P = 0.02, OR = 0.61). Importantly, the HTR2A (rs6313), GRIN2B (rs2268132), and GRIK5 (rs8099939) polymorphisms were only associated with COPD in smokers. Smoking index (pack-years) was significantly higher in carriers of the GRIK5 genotype AC (rs8099939) (P = 0.0027). The TT genotype of GRIN2B (rs2268132) was associated with COPD in subjects with high nicotine dependence according to the Fagerström test (P = 0.002, OR = 2.98). The TT genotype of HTR2A (rs6313) was associated with a reduced risk of the disease in the group with moderate nicotine dependence (P = 0.02, OR = 0.22). The CC genotype of HTR2A (rs6313) and the TT genotype of GRIN2B (rs2268132) were associated with higher levels of nicotine dependence according to the Fagerström test (P = 0.0011 and P = 0.037). Our results may provide insight into potential molecular mechanisms that involve the glutamate (GRIK5, GRIN2B) and serotonin (HTR2A) receptor genes in the pathogenesis of COPD.

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Abbreviations

COPD:

chronic obstructive pulmonary disease

VC:

vital capacity

FVC:

forced vital capacity

FEV1:

forced expiration volume in 1 second

FTND:

Fagerström test for nicotine dependence

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics, Ufa Scientific Center, Ufa, 450054, Russia

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

  2. Bashkortostan State Medical University, Ufa, 450000, Russia

    Y. 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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  4. Y. G. Aznabaeva
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  5. Sh. Z. Zagidullin
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  6. T. V. Victorova
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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, Y.G. Aznabaeva, Sh.Z. Zagidullin, T.V. Victorova, 2017, published in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 4, pp. 603–614.

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Korytina, G.F., Akhmadishina, L.Z., Kochetova, O.V. et al. Polymorphic variants of glutamate receptor (GRIK5, GRIN2B) and serotonin receptor (HTR2A) genes are associated with chronic. Mol Biol 51, 533–542 (2017). https://doi.org/10.1134/S0026893317040124

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