矽肺遗传易感性研究进展

Advances in research on genetic susceptibility to silicosis

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。

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.