Relationship Between TSLP And GLCCI1 Gene Polymorphisms And Asthma Susceptibility And GLCCI1 Gene Polymorphisms And ICSs Efficacy In Asthma Patients:a Meta-analysis

Objective:In this study,Meta-analysis was performed to combine the effect size of the genetic association studies that met the conditions,and to explore the influence of TSLP and GLCCI1 gene single nucleotide polymorphisms（SNPs）on the risk of asthma and the correlation between GLCCI1 gene SNPs and the efficacy of inhaled glucocorticoids（ICSs）in asthma patients,in order to provide some evidence-based evidence for the early recognition,risk prediction and individualized treatment of asthma.Methods:Pub Med,Embase,Cochrane Library,CNKI,VIP and Wan Fang databases were searched to obtain the literatures published before January 2023 on the association between TSLP,GLCCI1 gene SNPs and asthma susceptibility,and the association between GLCCI1 gene SNPs and ICSs efficacy in asthma patients.The literatures that met the inclusion and exclusion criteria were screened,and then the data extraction and quality evaluation were carried out for the literatures that met the requirements.Odds ratios（ORs）and mean difference（MD）were respectively the effect sizes of dichotomous variables and continuous variables,and the interval estimation was expressed with 95%confidence intervals（CIs）.The effect size was combined in Rev Man5.4 software.Results:A total of 28 articles were included,10 of which reported the association between TSLP gene SNPs（rs2289276,rs2289278,rs3806933,rs1837253）and asthma susceptibility,covering 10744 patients and 31055 healthy controls.There were 10studies on the association between GLCCI1 SNPs（rs37973,rs37972,rs37969）and asthma susceptibility,covering 2284 patients and 2350 controls.Eleven studies involving 1314 asthmatic patients were involved in the association between GLCCI1SNPs（rs37973,rs37972）and the efficacy of ICSs.Meta-analysis showed the CG+GG genotype and G allele of rs2289278 decreased the risk of asthma in dominant and allele models（CG+GG vs.CC,OR=0.86,95%CI=0.75～0.98,P=0.02;G vs.C,OR=0.87,95%CI=0.77～0.97,P=0.02）.The CT and CT+CC genotypes of rs1837253increased the risk of asthma in heterozygote,dominant and over-dominant models（CT vs.TT:OR=1.24,95%CI=1.05～1.46,P=0.009;CT+CC vs.TT:OR=1.27,95%CI=1.06～1.53,P=0.009;CT vs.CC+TT:OR=1.15,95%CI=1.02～1.30,P=0.02）.Rs3806933 SNP was associated with asthma risk in over-dominant model（CT vs.CC+TT:OR=1.15,95%CI=1.01～1.31,P=0.04）.There was no correlation between rs2289276 polymorphism and asthma risk（P>0.05）.In subgroup analysis,all of four SNPs loci on TSLP gene were associated with asthma susceptibility in Asian population（P<0.05）.The T allele of rs2289276 decreased the risk of asthma in Caucasians（T vs.C:OR=0.68,95%CI=0.51～0.90,P=0.007）and increased the risk of asthma in Asians（T vs.C,OR=1.28,95%CI=1.11～1.48,P<0.00001）.Rs2289276 and rs3806933 SNPs were found to be associated with asthma risk in children（P<0.05）.In the overall analysis,GLCCI1 gene rs37973,rs37972 and rs37969 polymorphisms were not associated with asthma susceptibility（P>0.05）,but in some models of inheritance（rs37973 loci:heterozygous and homozygous,dominant and over-dominant models;rs37972 loci:over-dominant model）rs37973 and rs37972 SNPs were significantly associated with the susceptibility to adult asthma（P<0.05）.In addition,for the effect of GLCCI1 gene SNPs on the efficacy of ICSs in asthma patients,the variation of rs37973 and rs37972 loci would reduce the improvement of lung function（FEV₁and FEV₁/Pre）after ICSs treatment in asthma patients（P<0.05）.Conclusions:The present study further confirmed that rs2289278 and rs1837253SNPs of TSLP gene were significantly associated with the risk of asthma by expanding sample size.The correlation between SNPs of GLCCI1 gene and asthma susceptibility was influenced by factors race and age.GLCCI1 gene rs37973 and rs37972polymorphisms are associated with the improvement of lung function after ICSs treatment in patients with asthma.Therefore,SNPs of the TSLP gene may act as potential biomarkers for the early diagnosis and risk prediction of asthma,while SNPs of GLCCI1 may act as potential biomarkers for predicting the response of asthma patients to ICSs.