Association between multidrug resistance-1 C3435T gene polymorphism and right ventricular dysfunction in patients with chronic obstructive pulmonary disease

cross-sectional study

Authors

Keywords:

Pulmonary disease, chronic obstructive, Polymorphism, genetic, Ventricular dysfunction, right, Circulation, Pulmonary

Abstract

BACKGROUND: Right ventricular (RV) dysfunction may develop over the course of chronic obstructive pulmonary disease (COPD) and is an important predictor of morbidity and mortality. Polymorphism of the multidrug resistance-1 (MDR-1) gene has been correlated with worse clinical findings among patients with COPD. Our aim here was to investigate the relationship between MDR-1 C3435T gene polymorphism and RV dysfunction in COPD patients. DESIGN AND SETTING: This was a cross-sectional study investigating the relationship between RV dysfunction and genetic defects in COPD patients. METHODS: Forty-one consecutive patients diagnosed with COPD and hospitalized due to acute exacerbation were enrolled. Polymorphism was analyzed using the strip assay technique. RV parameters were evaluated, and RV dysfunction was identified via transthoracic echocardiography. Patients were categorized into three groups according to gene polymorphism: MDR-1 CC (wild type, n = 9), MDR-1 CT (heterozygote mutant, n = 21) or MDR-1 TT (homozygote mutant, n = 11). RESULTS: The study included 14 males and 27 females (mean age 65 ± 11 years). The mean systolic pulmonary artery pressure was 31.4 ± 8 mmHg in the wild-type group, 42.2 ± 12 mmHg in the heterozygote mutant group and 46.5±14 mmHg in the homozygote mutant group (P = 0.027). Presence of RV dilatation was significantly different among the three groups (33%, 71%, and 100%, respectively; P = 0.005). In multiple logistic regression analysis, MDR-1 C3435T gene polymorphism (OR = 9.000, P = 0.019) was an independent predictor of RV dysfunction after adjustment for potential confounders. CONCLUSION: MDR-1 C3435T gene polymorphism was associated with RV dysfunction in patients with COPD.

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Author Biographies

Hakan Güneş, Department of Cardiology, Kahramanmaraş Sütçü İmam Üniversitesi

MD. Assistant Professor, Department of Cardiology, Kahramanmaraş Sütçü İmam Üniversitesi, Kahramanmaraş, Turkey.

Hasan Yücel, Department of Cardiology, Kahramanmaraş Sütçü İmam Üniversitesi

MD. Associate Professor, Department of Cardiology, Cumhuriyet Üniversitesi Tıp Fakültesi, Sivas, Turkey.

Ali Zorlu, Department of Cardiology, Kahramanmaraş Sütçü İmam Üniversitesi

MD. Associate Professor, Department of Cardiology, Cumhuriyet Üniversitesi Tıp Fakültesi, Sivas, Turkey.

References

Kardos P, Keenan J. Tackling COPD: a multicomponent disease driven by inflammation. MedGenMed. 2006;8(3):54. PMID: 17406181.

Regan EA, Hokanson JE, Murphy JR, et al. Genetic epidemiology of COPD (COPDGene) study design. COPD. 2010;7(1):32-43. doi: 10.3109/15412550903499522.

Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2645-53. doi: 10.1056/NEJMoa032158.

Toru U, Ayada C, Genç O, et al. MDR-1 gene C/T polymorphism in COPD:data from Aegean part of Turkey. Int J Clin Exp Med. 2014;7(10):3573-7. PMID: 25419400.

Sharom FJ. ABC multidrug transporters: structure, function and role in chemoresistance. Pharmacogenomics. 2008;9(1):105-27. doi: 10.2217/14622416.9.1.105.

van der Deen M, Marks H, Willemse BW, et al. Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients. Virchows Arch. 2006;449(6):682-8. doi: 10.1007/s00428-006-0240-3.

Budulac SE, Postma DS, Hiemstra PS, et al. Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD. Respir Res. 2010;11:60. doi: 10.1186/1465-9921-11-60.

Lepper ER, Nooter K, Verweij J, et al. Mechanisms of resistance to anticancer drugs: the role of the polymorphic ABC transporters ABCB1 and ABCG2. Pharmacogenomics. 2005;6(2):115-38. doi: 10.1517/14622416.6.2.115.

Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685-713; quiz 786-8. doi: 10.1016/j.echo.2010.05.010.

Lancellotti P, Moura L, Pierard LA, et al. European Association of Echocardiography. European Association of Echocardiography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). Eur J Echocardiogr. 2010;11(4):307-32. doi: 10.1093/ejechocard/jeq031.

Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984;70(4):657-62. PMID: 6478568.

Oswald-Mammosser M, Weitzenblum E, Quoix E, et al. Prognostic factors in COPD patients receiving long-term oxygen therapy: Importance of pulmonary artery pressure. Chest. 1995;107(5):1193-8. PMID: 7750305.

Kessler R, Faller M, Fourgaut G, Mennecier B, Weitzenblum E. Predictive factors of hospitalization for acute exacerbation in a series of 64 patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;159(1):158–64. doi: 10.1164/ajrccm.159.1.9803117.

Dogan OT, Katrancıoglu N, Karahan O, et al. Frequency of the MDR-1 C>T gene polymorphism in patients with COPD. Clinics (Sao Paulo). 2010;65(11):1115-7. PMID: 21243282.

Siedlinski M, Boezen H, Boer JM, et al. ABCC1 polymorphisms contribute to level and decline of lung function in two population-based cohorts. Pharmacogenet Genomics. 2009;19(9):675-84. PMID: 21243282.

van der Deen M, de Vries EG, Visserman H, et al. Cigarette smoke extract affects functional activity of MRP1 in bronchial epithelial cells. J Biochem Mol Toxicol. 2007;21(5):243-51. doi: 10.1002/jbt.20187.

Izzotti A, Cartiglia C, Longobardi M, et al. Alterations of gene expression in skin and lung of mice exposed to light and cigarette smoke. FASEB J. 2004;18(13):1559-61. doi: 10.1096/fj.04-1877fje.

Papp E, Gadawski I, Côté HC. Longitudinal effects of thymidine analogues on mtDNA, mtRNA and multidrug resistance (MDR-1) induction in cultured cells. J Antimicrob Chemother. 2008;61(5):1048-52. doi: 10.1093/jac/dkn067.

Israeli D, Ziaei S, Gonin P, Garcia L. A proposal for the physiological significance of mdr1 and Bcrp1/Abcg2 gene expression in normal tissue regeneration and after cancer therapy. J Theor Biol. 2005;232(1):41-5. doi: 10.1016/j.jtbi.2004.07.018.

Drach J, Gsur A, Hamilton G, et al. Involvement of P-gp in the transmembrane transport of IL-2,IL-4 and IFN-c in normal human T lymphocytes. Blood. 1996;88(5):1747-54. PMID: 8781431.

Piquette-Miller M, Pak A, Kim H, Anari R, Shahzamani A. Decreased expression and activity of P-glycoprotein in rat liver during acute inflammation. Pharm Res. 1998;15(5):706-11. PMID: 9619778.

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Published

2018-04-05

How to Cite

1.
Yücel O, Güneş H, Yücel H, Zorlu A. Association between multidrug resistance-1 C3435T gene polymorphism and right ventricular dysfunction in patients with chronic obstructive pulmonary disease: cross-sectional study. Sao Paulo Med J [Internet]. 2018 Apr. 5 [cited 2025 Mar. 14];136(2):140-3. Available from: https://periodicosapm.emnuvens.com.br/spmj/article/view/1357

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