基质金属蛋白酶⁃9 rs3918242、rs17576位点基因多态性与矽肺易感性的关系
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国家自然科学基金(81673119)


Association of matrix metalloproteinases⁃9 gene polymorphisms at rs3918242 and rs17576 with susceptibility to silicosis
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    目的:探讨基质金属蛋白酶(matrix metalloproteinases,MMP)-9 rs3918242、rs17576位点基因多态性与湖南郴州地区某锡矿男性接尘作业人员矽肺易感性的关系。方法:采用1∶1配对病例-对照研究方法,以确诊的186例矽肺患者为病例组,以健康接尘工人为对照组,按同年龄、同性别、同工种、相同累计接尘工龄进行配对,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测MMP-9基因 rs3918242与rs17576两位点基因型,用酶联免疫吸附试验(ELISA)测定外周血MMP-9水平。结果:病例组MMP -9 rs3918242位点C/C、C/T、T/T基因型频率分别为38.7%、34.4%、26.9%,C、T等位基因频率分别为55.9%、44.1%,对照组C/C、C/T、T/T基因型频率分别为57.5%、25.8%、16.7%,C、T等位基因频率分别为70.4%、29.6%,两组基因型与等位基因频率分布差异均有统计学意义(P < 0.05),且病例组C/T、T/T基因型以及T等位基因频率均显著高于对照组。rs17576 位点基因型与等位基因频率在两组间分布的差异均无统计学意义(P > 0.05)。Ⅱ、Ⅲ期矽肺病例组T等位基因频率显著高于对照组,携带T等位基因群体外周血MMP-9水平显著高于CC基因型群体。结论:MMP -9 rs 3918242位点基因多态性可能与矽肺发生及其严重程度有关,而rs17576位点基因多态性可能与矽肺易感性无关。

    Abstract:

    Objective:To investigate the relationship between polymorphisms of matrix metalloproteinases(MMP)-9(rs3918242 and rs17576)and silicosis susceptibility of male workers who exposed to industrial dust with silicosis in Hongzhou,Hunan province. Methods:This case-control study included 186 silicosis patients and 186 individuals exposed to industrial dust but without silicosis(the control group),who were strictly matched with the case group for age,gender,work type and cumulative length of dust exposure. The rs3918242 and rs17576 polymorphisms of MMP-9 were detected in all participants using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Meanwhile,plasma levels of total MMP-9 were analyzed by ELISA. Results:Frequencies of C/C,C/T and T/T genotypes of MMP-9 rs3918242 locus were 38.7%,34.4%,and 26.9% in the case group,significantly different from frequencies of 57.5%,25.8%,and 16.7% in the control group,respectively(P < 0.05). Frequencies of C and T alleles were 55.9% and 44.1% in the case group,significantly different from frequencies of 70.4% and 29.6% in the control group,respectively(P < 0.05). Frequencies of C/T,T/T genotype and T allele in the case group were significantly higher than those in the control group. There was no significant difference in the distribution of rs17576 loci genotype and allele frequency between two groups(P > 0.05). Furthermore,frequencies of T allele of silicosis patients in theⅡand Ⅲ stages were significantly higher than those of the control group,and circulating levels of total MMP-9 were also significantly higher in subjects with T allele than those in subjects with CC genotype. Conclusion:MMP-9 rs3918242 polymorphism is significantly associated with silicosis and the severity of pulmonary fibrosis,and the polymorphism of rs17576 loci may not be related to silicosis susceptibility.

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吴传文,陈 鹏,隆素素,刘和亮.基质金属蛋白酶⁃9 rs3918242、rs17576位点基因多态性与矽肺易感性的关系[J].南京医科大学学报(自然科学版),2019,(3):349-354

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  • 收稿日期:2018-04-09
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  • 在线发布日期: 2019-04-01
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