Clinical Implications of LTA₄H Genetic Polymorphism in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Leukotriene A₄ hydrolase (LTA₄H) is associated with inflammation and emphysema. Nevertheless, clinical implications of LTA₄H genetic polymorphism in chronic obstructive pulmonary disease (COPD) has been understudied to date. A prospective study was performed to investigate the clinical implications of LTA₄H genetic polymorphism in patients with COPD. AA, GA, and GG types of genetic polymorphism of LTA₄H were assayed in patients with COPD at the baseline. Then all patients were followed up for 12 months. At the baseline, the number of participants with AA, GA, and GG type of LTA₄H rs7971150 were 22 (14.2%), 43 (27.7%), and 90 (58.1%) in the COPD group (n = 155), whereas 55 (36.7%), 38 (25.3%), and 57 (38.0%) in the control group (n = 150) (p = 0.001). During the follow-up, the variations with respect to forced expiratory volume in one second (FEV₁), 6 min walking distance (6MWD), and BODE (body-mass index, obstruction, dyspnea, and exercise capacity) were similar between patients with AA and GA types, which were both lower than those of GG type. The patients with GG type had more hospitalizations than patients with AA (p = 0.001) and GA (p = 0.001) types, respectively. The cumulative hospitalization-free rate in patients with GG type was lower than those of patients with AA and GA types, respectively (p = 0.019). Compared with COPD patients with AA and GA types, patients with GG type were positively correlated with smoking, more hospitalizations, worse FEV₁, 6MWD, and BODE index. The current study suggests that GG type of LTA4H is a predisposing factor in COPD development, functional decline, and exacerbation of patients with COPD.

Keywords:

• Chronic obstructive pulmonary disease
• genetic polymorphism
• LTA₄H
• clinical implications

Acknowledgements

We are indebted to all the participants involved in this study.

Authors’ contributions

YFZ and WX were in full charge of the design and performance of the study, the analysis and interpretation of the data, and the writing of the manuscript. MX, ML, and QZ contributed more or less to the study design, data analysis and interpretation, and the writing of the manuscript. All authors have read and approved the final manuscript.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declaration of interest

The authors declare no competing interests.

Additional information

Funding

This study was funded by Key Specialty Training Program of Health System of Shanghai Pudong New District (PWZZK2017-18); Leading Talents Training Program of Health System of Shanghai Pudong New District (PWRL2017-01)