Department of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 510025, China.
Sci Rep. 2021 Dec 14;11(1):24007. doi: 10.1038/s41598-021-03533-z.
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.
MUC5B 启动子 rs35705950 T/G 基因多态性与特发性肺纤维化(IPF)的风险相关,但这种关系在不同人群中的影响有所不同。在过去的 2 年中,有新的临床研究得出了不同的结果,但没有一项研究得出统一的结论。因此,本研究进一步纳入了最新的病例对照研究,整合了它们的结果,并对它们进行了荟萃分析,以得出可靠的结论。计算机检索 PubMed、EMBASE、CNKI、万方数据库和 VIP 中文科技期刊数据库,收集截至 2021 年 6 月 15 日发表的关于 MUC5B 基因多态性与 IPF 易感性相关的文献。筛选后提取第一作者、发表年份、诊断标准和基因频率。绘制森林图并进行试验序贯分析(TSA),以确认荟萃分析结果的稳定性。注册号:CRD42021272940。共纳入 24 项病例对照研究(13 项研究针对白种人,7 项研究针对亚洲人,4 项研究针对混合人群),共纳入 6749 例 IPF 患者和 13898 例健康对照。MUC5B 启动子 rs35705950 T/G 多态性的 T vs. G、TT vs. GG、GT vs. GG、GT+TT vs. GG 和 TT vs. GG+GT 遗传模型均与所有人群的 IPF 风险相关,效应值分别为(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])和(OR)5.11,95%CI[4.02,6.49])。TSA 的结果证实了结果的稳定性。亚组分析显示,MUC5B 多态性的 T vs. G、TT vs. GG、GT vs. GG、GT+TT vs. GG 和 TT vs. GG+GT 遗传模型与白种人 IPF 风险相关。效应值分别为(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])和(OR)5.15,95%CI[4.01,6.61])。在亚洲人和混合人群中也发现了类似的结果。白种人次要 T 等位基因的关联强度比亚洲人更显著(OR)4.50 vs. (OR)2.39),并且所有携带“T”的遗传模型的关联强度比亚洲人更显著(OR)10.98 vs. (OR)4.29)。在白种人、亚洲人和混合人群中,携带 T 等位基因的个体更易患肺纤维化,携带 TT 基因型的个体比携带 GT 基因型的个体更易患 IPF。与亚洲人群相比,MUC5B 启动子 rs35705950 T/G 多态性与白种人群中携带 T 等位基因和所有“T”遗传模型的 IPF 相关性更显著。