Abstract
MUC5B promoter rs35705950 T/G gene polymorphism has been associated with the risk of IPF, but the influence of this relationship varies among different populations. In the past 2 years, there were new clinical studies with different results, but none of them reached unified conclusions. Therefore, this study further included the latest case–control studies, integrated their results and carried out meta-analysis on them to draw reliable conclusions. PubMed, EMBASE, CNKI, Wanfang database and VIP Chinese science were searched by a computer to collect the related literatures of MUC5B gene polymorphism and IPF susceptibility published before June 15, 2021. The first author, year of publication, diagnostic criteria and gene frequency were extracted after screened them. Forest plot was drawn and the trial sequential analysis (TSA) was carried out to confirm the stability of the meta-analysis results. Registration number: CRD42021272940. A total of 24 case–control studies (13 studies on the Caucasian, 7 studies on the Asian and 4 studies on the mixed population), and a total of 6749 IPF patients and 13,898 healthy controls were included in this study. The T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B promoter rs35705950 T/G polymorphism were associated with IPF risk in all populations, and the effect values were ([OR] 4.12, 95% CI [3.64, 4.67]), ([OR] 10.12, 95% CI [7.06, 14.49]), ([OR] 4.84, 95% CI [3.85, 6.08]), ([OR] 4.84, 95% CI [3.79, 6.19]) and ([OR] 5.11, 95% CI [4.02, 6.49]), respectively. The results of TSA confirmed the stability of the results. Subgroup analysis showed that T vs.G, TT vs. GG, GT vs. GG, GT + TT vs. GG and TT vs. GG + GT genetic models of MUC5B polymorphism were associated with IPF risk in Caucasian population. The effect values were ([OR] 4.50, 95% CI [3.93, 5.16]), ([OR] 10.98, 95% CI [7.59, 15.89]), ([OR] 6.27, 95% CI [5.37, 7.32]), ([OR] 6.30, 95% CI [5.19, 7.64]) and ([OR] 5.15, 95% CI [4.01, 6.61]), respectively. Similar results were also found in Asian and mixed populations. The association strength of the minor T allele in the Caucasian was more significant than that of the Asian population ([OR] 4.50 vs. [OR] 2.39), and the association strength of all genetic models carrying "T" was more significant than that of the Asian population ([OR] 10.98 vs. [OR] 4.29). In Caucasian, Asian and mixed populations, T minor allele carriers were more likely to be susceptible to pulmonary fibrosis, and TT genotype carriers were more likely to be susceptible to IPF than GT genotype carriers. The association between IPF and Caucasian population with minor T allele and all "T" genetic model was more significant than that of Asian population.
Highlights
95% CI 95% Confidence interval ATS American thoracic society ERS European respiratory society JRS Japanese respiratory society ALAT Latin American thoracic society NOS Newcastle Ottawa scale required information size (RIS) Required information size OS Average overall survival PCR Polymerase chain reaction HWE Hardy Weinberg equilibrium
Meta-analysis has showed that comparing with G allele, minor T allele was associated with increased risk of Idiopathic pulmonary fibrosis (IPF), TT genotype carriers were more prone to IPF than GT genotype carriers, and the association strength of Caucasian population was more significant than that of Asian population24–26.in the past two years, there were new clinical studies reporting the correlation between rs35705950 and IPF, and their research results were different, so there was no unified statement
(1) The case–control studies are all based on the susceptibility of Mucin 5B (MUC5B) rs35705950 T/G gene polymorphism and IPF; the language is either Chinese or English; the description of detection methods and means is accurate; (2) They conform to the authoritative standards established by the Chinese Society of Respiratory Medicine[2] or the ATS/ERS/JRS/ALAT1.The patients were not limited in gender, age, race and nationality, and other serious systemic diseases were excluded; (3) The gene frequency data is complete and can be used to calculate the OR and 95% CI; (4) The distribution of genotype frequency of all subjects conformed to Hardy–Weinberg equilibrium[28]; (5) The score of Newcastle Ottawa scale (NOS)[29] was no less than 7(≧7)
Summary
95% CI 95% Confidence interval ATS American thoracic society ERS European respiratory society JRS Japanese respiratory society ALAT Latin American thoracic society NOS Newcastle Ottawa scale RIS Required information size OS Average overall survival PCR Polymerase chain reaction HWE Hardy Weinberg equilibrium. Mucin 5B (MUC5B) played an important role in immune regulation in maintaining bronchoalveolar epithelial function, and its genetic variation had been identified as a risk factor for I PF5,6.So far, Genome-wide Association Study (GWAS) has found a SNP in the promoter region of MUC5B gene (rs35705950), in which the T allele frequency was 30–35% in IPF cases[6,7,8,9,10,11,12,13,14].Variant rs35705950 alone explains 5.9–9.4% of disease liability in the general population and 13.5% in people > 65 years of a ge[15]. The same study published many times, only the one with the largest sample size and the most complete information was reserved
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