摘要
职业性矽肺(以下简称"矽肺")发病情况存在个体差异,遗传因素在矽肺的发生发展中扮演重要角色.其中,细胞因子如白细胞介素(IL)-1RA基因+2018T>C位点、肿瘤坏死因子-α基因-308G>A和-238G>A位点、转化生长因子(TGF)-β1+915G>C位点与矽肺发生存在相关关系,IL-17F基因+7488A>G和TGF-β1基因-509T>C位点与矽肺的关联在不同研究中的结论不一致.调控蛋白如基质金属蛋白酶(MMP)-2基因-735C>T位点、MMP-9 rs3918242位点、热休克蛋白 70-1 基因+190G>C位点、羧肽酶M rs12812500位点、家族序列相似性基因13A(FAM13A)rs2609255位点、桥粒蛋白rs2076304位点也与矽肺的发展存在相关关系.非编码RNA微小RNA-4508 rs6576457的A等位基因增加了接触粉尘劳动者罹患矽肺相关肺纤维化的风险;长链非编码RNA黏附G蛋白偶联受体3基因中rs1814521多态性与矽肺易感性存在相关关系;小核仁RNA宿主基因14 rs17115143基因序列对应的6个环状RNAs可能是潜在的矽肺生物标志物.人类白细胞抗原-DR基因与矽肺的关系具有危险和保护的双重作用;血管紧张素Ⅰ转换酶(ACE)基因多态性可能通过影响血清ACE活力进而影响矽肺的发展.然而,部分基因的遗传变异对矽肺易感性的作用机制并不明确.未来需结合遗传学、流行病学、生物信息学、生物学功能研究,进行大样本的前瞻性研究,以促进矽肺易感性和病程的生物标志物研究与临床治疗方法的发展.
Abstract
Occupational silicosis(hereinafter referred to as"silicosis")exhibited individual differences in disease susceptibility,with genetic factors playing a crucial role in its onset and progression.Cytokines,such as interleukin(IL)-1RA+2018T>C locus,tumor necrosis factor-α-308G>A and-238G>A locus,transforming growth factor(TGF)-β1+915G>C locus,were related to the development of silicosis.However,relationship between IL-17F+7488A>G and TGF-β1-509T>C locus with silicosis had shown inconsistent results across different studies.Regulatory proteins such as matrix metalloproteinase(MMP)-2-735C>T locus,MMP-9 rs3918242 locus,heat shock protein(HSP)70-1+190G>C locus,carboxypeptidase M rs12812500 locus,family sequence similarity gene 13A(FAM13A)rs2609255 locus,and desmoplakin rs2076304 locus were also related to the development of silicosis.The A allele of the non-coding RNA miRNA-4508 rs6576457 increased the risk of developing silicosis-related pulmonary fibrosis in dust-exposed workers.The polymorphism in the long non-coding RNA ADGRG3 rs1814521 was related to silicosis susceptibility.Additionally,six circular RNAs of small nucleolar RNA host gene 14 rs17115143 sequence might be potential biomarkers of silicosis.Human leukocyte antigen-DR(HLA-DR)genes demonstrated a dual role in both risk and protection against silicosis,while angiotensin I-converting enzyme(ACE)gene polymorphisms likely affected silicosis development by modulating serum ACE activity.However,the mechanisms by which certain genetic variations affected susceptibility to silicosis remain unclear.Prospective studies with large-scale samples combining genetics,epidemiology,bioinformatics,and biofunctional studies are needed to promote the development of biomarkers for silicosis susceptibility and disease course,and clinical therapies.
基金项目
江苏省自然科学基金面上项目(BK20211038)
江苏省卫生健康委2019年度医学科研项目(H2019020)
NETL
NSTL
万方数据