白细胞介素相关基因多态性与尘肺易感性系统评价与meta分析

目的综合分析白介素(interleukin,IL)相关基因多态性与尘肺病的易感关联性。方法检索PubMed、the Cochrane Library、Embase、中国知网、WanFang Data、VIP、CBM等数据库,检索时间为建库至2022年1月8日。2名研究者独立提取资料并评价文献偏倚风险。采用RevMan 5.2以及Stata 14.0软件,分别以等位基因模型、显性模型、隐性模型、共显性模型(2种)、超显性模型等对IL相关基因多态性与尘肺病易感的关联进行meta分析。结果共纳入29篇文献,共计尘肺病例组5315例,对照组5332例。8项关于IL-1β(-511)C/T多态位点meta分析结果显示,隐性模型(OR=1.57,95%CI=1.06~2.33,P=0.024)、共显性模型TT vs CC(OR=1.80,95%CI=1.03~3.13,P=0.039)与尘肺的易感风险相关。6项关于IL-1RA(+2018)T/C多态性分析结果显示,等位基因模型(OR=1.65,95%CI=1.21~2.27,P=0.002)、显性模型(OR=1.65,95%CI=1.11~2.46,P=0.013)、隐性模型(OR=2.14,95%CI=1.50~3.06,P=0.000)、共显性模型(CC vs TT)(OR=2.29,95%CI=1.58~3.32,P=0.000)与尘肺的易感风险有关。4项有关IL-1α(-889)C/T多态位点的meta分析结果显示,显性模型(OR=1.75,95%CI=1.02~3.01,P=0.042)、共显性模型CT vs CC(OR=1.79,95%CI=1.21~2.636,P=0.004)与尘肺的易感风险相关。3项关于IL-1α(+4845)G/T多态位点的meta分析结果显示,等位基因模型(OR=1.59,95%CI=1.03~2.56,P=0.038)与尘肺的易感风险相关。4项关于IL-6(-634)C/G多态位点的meta分析结果显示等位基因模型(OR=0.60,95%CI=0.47~0.75)、显性模型(OR=0.47,95%CI=0.35~0.64)、共显性模型(OR=0.63,95%CI=0.42~0.94)(OR=0.36,95%CI=0.24~0.54)、超显性模型(OR=2.51,95%CI=1.71~3.69)与尘肺的易感风险有关。2项研究meta分析结果显示,IL-8(781)C/T、IL-8 Met31Arg T/G、IL-8(-251)A/T多态性与尘肺的易感风险有关联。而IL-1β(+3953)C/T、IL-6(-174)G/C、IL-10(-592)A/C多态位点及其他白介素相关基因的多种基因模型的分析结果均显示与尘肺的易感风险无关。结论IL-1RA(+2018)T/C、IL-6(-634)C/G多态位点与尘肺的易感风险显著相关;IL-1α(+4845)G/T、IL-1β(-511)C/T、IL-1α(-889)C/T多态位点与尘肺的易感风险可能有关;IL-1β(+3953)C/T、IL-6(-174)G/C多态位点与尘肺病的易感风险无关联;后续仍需多中心大样本量的研究进一步探讨分析。

Correlation between the gene polymorphisms of interleukin and the susceptibility to pneumonoconiosis: A systematic review and meta-analysis

Objective To investigate the correlationbetween the genepolymorphisms of interleukin and the susceptibility to pneumonoconiosis. Methods Literatures reporting the correlation between the gene polymorphisms of interleukin and the susceptibility to pneumonoconiosis in the PubMed, the Cochrane Library, Embase, CNKI, Wanfang Data, Weipu Database (VIP), and Chinese Biomedical Database (CBM) and other databases, which were published from the establishment of the databases to January 8, 2022 were screened.Two researchers independently extracted data and assessed the risk of bias. Using RevMan 5.2 and Stata 14.0, allelic model, dominant model, recessive model, co-dominant models (2 models), and over-dominant model were used in the meta-analysis on the correlation between interleukin-associated gene polymorphisms and susceptibility to pneumoconiosis. Results A total of 29 eligiblestudies, involving 5 315 pneumoconiosis cases and 5 332 controls were included in the current study. There were 8 literatures reporting the IL-1β-511C/T polymorphism, and the data revealed that the recessive model (OR=1.57, 95%CI=1.06-2.33, P=0.024), and co-dominant model (TT vs CC) (OR=1.80, 95%CI=1.03-3.13, P=0.039) of the IL-1β-511C/T polymorphism were significantly correlated with the susceptibility to pneumonoconiosis. There were 6 literatures reporting the IL-1RA+2018T/C polymorphism, and the data revealed that the allele model(OR=1.65, 95%CI=1.21-2.27, P=0.002), dominant model(OR=1.65, 95%CI=1.11-2.46, P=0.013), recessive model(OR=2.14, 95%CI=1.50-3.06, P=0.000), and co-dominant model (TT vs CC) (OR=2.29, 95% CI=1.58-3.32, P=0.000) of the IL-1RA+2018T/C polymorphism were significantly correlated with the susceptibility to pneumonoconiosis. There were 4 literatures reporting the IL-1α-889C/T polymorphism, and the data revealed that the dominant model(OR=1.75, 95%CI=1.02-3.01, P=0.042), and co-dominant model (CT vs CC)(OR=1.79, 95%CI=1.21-2.636, P=0.004) of the IL-1α-889C/T polymorphism were significantly correlated with the susceptibility to pneumonoconiosis. There were 3 literatures reporting the IL-1α +4845G/T polymorphism, and the data revealed that the allele model(OR=1.59, 95%CI=1.03-2.56, P=0.038) of the IL-1α+4845G/T polymorphism was significantly correlated with the susceptibility to pneumonoconiosis. There were 4 literatures reporting the IL-6 -634C/G polymorphism, and the data revealed that the allele model(OR=0.60, 95%CI=0.47-0.75), dominant model(OR=0.47, 95% CI=0.35-0.64), co-dominant model(OR=0.63, 95%CI=0.42-0.94) (OR=0.36, 95%CI=0.24-0.54) and over-dominant model (OR=2.51, 95%CI=1.71-3.69) of the IL-6 -634C/G polymorphism were significantly correlated with the susceptibility to pneumonoconiosis. There were 2 literatures reporting the IL-8 -781C/T, IL-8-Met31Arg T/G and IL-8 -251A/T polymorphisms, and the data revealed their significant correlation with thesusceptibility to pneumonoconiosis. There was no significant correlation between IL-1β +3953C/T, IL-6 -174G/C and IL-10 -592A/C polymorphisms with the susceptibility topneumoconiosis. Conclusion IL-1RA +2018T/C and IL-6 -634 C/G polymorphisms were significantly correlated with the susceptibility to pneumoconiosis. IL-1α +4845G/T, IL-1β -511C/T and IL-1α -889C/T polymorphisms may be correlated with the susceptibility to pneumoconiosis. IL-1β +3953C/T and IL-6 -174G/C were not correlated with the susceptibility to pneumoconiosis. Our findings should be further validated in multi-center studies with a large sample size.