Association of cytoplasmic phospholipase A2 gene polymorphism with bronchial asthma and response to montelukast in children
GUO Qing1, SHEN Zhao-Bo2, SUN Xiao-Min1, CHEN Dan1, KANG Ping2
Department of West District General Internal Medicine, Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital/Zhengzhou Children's Hospital, Zhengzhou 450000, China
Abstract Objective To study the association of cytoplasmic phospholipase A2 (PLA2G4) rs932476 polymorphism with the development of bronchial asthma and the response to montelukast, a leukotriene receptor antagonist, in children. Methods A total of 128 children with bronchial asthma were enrolled as case group, and 100 healthy children were enrolled as control group. The genotype and allele frequencies of PLA2G4 rs932476 were compared between the two groups. The children in the case group were administered with montelukast except routine treatment for 2 months, and the changes in serum levels of leukotriene B4 (LTB4), interleukin-4 (IL-4), immunoglobulin E (IgE), and interferon gamma (IFN-γ), pulmonary function and fractional exhaled nitric oxide (FeNO) after treatment were observed. Results There were no significant differences in the genotype and allele frequencies of PLA2G4 rs932476 between the case and control groups, as well as between the groups with different severities of asthma (P > 0.05). After treatment, the children with AA genotype had a significantly higher overall response rate than those with GG genotype. After treatment, the case group had significant reductions in the serum levels of IgE and IL-4 and a significant increase in the level of IFN-γ (P < 0.05). After treatment, the children with GG genotype had a higher serum level of IL-4 and a lower level of IFN-γ than those with AA genotype. After treatment, the case group had significant increases in pulmonary function parameters, and the children with AA genotype had significantly higher parameters than those with GG genotype. The case group had a significant reduction in the level of FeNO, and the children with AA genotype had a significantly lower level than those with GG genotype after treatment. The case group had a significantly higher serum level of LTB4 than the control group before treatment (P < 0.05). After treatment the case group had a significant reduction in the serum level of LTB4 (P < 0.05). The children with GG genotype had a significantly higher level of LTB4 than those with AA genotype after treatment (P < 0.05). Conclusions PLA2G4 rs932476 polymorphism is not associated with the susceptibility and severity of bronchial asthma in children, but it may has certain influence on children's response to the leukotriene receptor antagonist montelukast, possibly by affecting the level of LTB4.
GUO Qing,SHEN Zhao-Bo,SUN Xiao-Min et al. Association of cytoplasmic phospholipase A2 gene polymorphism with bronchial asthma and response to montelukast in children[J]. CJCP, 2019, 21(2): 155-160.
GUO Qing,SHEN Zhao-Bo,SUN Xiao-Min et al. Association of cytoplasmic phospholipase A2 gene polymorphism with bronchial asthma and response to montelukast in children[J]. CJCP, 2019, 21(2): 155-160.
Boyce JA, Barrett NA. Cysteinyl leukotrienes:an innate system for epithelial control of airway smooth muscle proliferation?[J]. Am J Respir Crit Care Med, 2015, 191(5):496-497.
[3]
Liu M, Yokomizo T. The role of leukotrienes in allergic diseases[J]. Allergol Int, 2015, 64(1):17-26.
Su KP, Huang SY, Peng CY, et al. Phospholipase A2 and cyclooxygenase 2 genes influence the risk of interferon-α-induced depression by regulating polyunsaturated fatty acids levels[J]. Biol Psychiatry, 2010, 67(6):550-557.
[12]
Yu Y, Zhang M, Pan Y, et al. PLA2G4A mutants modified protective effect of tea consumption against colorectal cancer[J]. Int J Colorectal Dis, 2012, 27(8):1005-1013.
[13]
de Jong K, Vonk JM, Imboden M, et al. Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure[J]. Respir Res, 2017, 18(1):142.
[14]
Rava M, Ahmed I, Kogevinas M, et al. Genes interacting with occupational exposures to low molecular weight agents and irritants on adult-onset asthma in three European studies[J]. Environ Health Perspect, 2017, 125(2):207-214.
[15]
Lee IT, Lin CC, Cheng SE, et al. TNF-α induces cytosolic phospholipase A2 expression in human lung epithelial cells via JNK1/2-and p38 MAPK-dependent AP-1 activation[J]. PLoS One, 2013, 8(9):e72783.
[16]
Pniewska E, Sokolowska M, Kupryś-Lipińska I, et al. The step further to understand the role of cytosolic phospholipase A2 alpha and group X secretory phospholipase A2 in allergic inflammation:pilot study[J]. Biomed Res Int, 2014:670814.
[17]
Hallstrand TS, Lai Y, Hooper KA, et al. Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils[J]. J Allergy Clin Immunol, 2016, 137(1):268-277. e8.
[18]
Song W, Zhang Y, Wang J, et al. Antagonism of cysteinyl leukotriene receptor 1(cysLTR1) by montelukast suppresses cell senescence of chondrocytes[J]. Cytokine, 2018, 103:83-89.
