HOGG1基因多态性对铬酸盐职业接触人群尿8-OHdG水平的影响
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摘要
目的评价铬酸盐职业接触对机体遗传损伤的影响,分析8-羟基鸟嘌呤DNA糖苷酶(hOGG1)基因多态性与铬酸盐致遗传损伤的关联。方法采用判断抽样方法,以136名铬酸盐作业工人为接触组,以156名无铬酸盐及其他职业病危害因素接触人员为对照组,采用电感耦合等离子体-质谱法测定2组人群周围血全血铬水平,以酶联免疫吸附试验测定尿8-羟基-脱氧鸟苷(8-OHdG)水平,采用基质辅助激光解析电离飞行时间质谱法对hOGG1基因4个单核苷酸多态性位点进行分型检测。结果接触组人群全血铬和尿8-OHdG水平均高于对照组(中位数:3.41 vs 0.90μg/L,6.02 vs 4.72μg/g肌酐,P<0.01)。对于研究对象(接触组和对照组人群),校正年龄、体质指数、性别、吸烟、饮酒等混杂因素后,铬酸盐接触可能为尿8-OHdG水平升高的危险因素(P<0.05);隐性模型下hOGG1的rs293796和rs13096551均为尿8-OHdG水平升高的危险因素(P<0.05)。对于接触组人群,校正年龄、体质指数、性别、吸烟、饮酒等混杂因素后,hOGG1的rs293796加性模型、隐性模型和rs13096551隐性模型均为尿8-OHdG水平升高的危险因素(P<0.05),rs3219008显性模型为尿8-OHdG水平升高的保护因素(P<0.05);但经Bonferroni多重检验校正后,仅rs293796隐性模型仍为接触组人群尿8-OHdG水平升高的危险因素(P<0.001),且与铬酸盐接触存在有统计学意义的交互作用(P<0.001)。结论 hOGG1基因rs13096551、rs293796与铬酸盐所致尿8-OHdG水平改变存在关联;rs293796和铬酸盐接触可交互影响机体尿8-OHdG水平。
Objective To evaluate the genetic damage induced by occupational chromate exposure, and to analyze the association between human 8-oxoguanine-DNA N-glycosylase 1(hOGG1) polymorphisms and genetic damage in population with chromate exposure. Methods A total of 136 chromate exposed workers were recruited as exposure group by judgmental sampling method, and 156 workers without chromate and other occupational hazard factors exposure were recruited as control group. The whole blood chromium(WB-Cr) level was measured by inductively coupled plasma mass spectrometry. Urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG) was determined by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms of hOGG1 gene were genotyped by the matrix assisted laser desorption ionization/time of flight mass spectrometry. Results The WB-Cr level was higher in the exposure group than that in the control group(meclian: 3.41 vs 0.90 μg/L, P<0.01). The urinary 8-OHdG level was higher in the exposure group compared with that in the control group(meclian: 6.02 vs 4.72 μg/g·creatinine, P<0.01). In study subjects(exposure group and control group), after adjusting the potential influencing factors such as age, body mass index(BMI), gender, smoking and drinking, chromate exposure might be a risk factor for increasing urinary 8-OHdG level(P<0.05), and the recessive models of rs293796 and rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05). In chromate exposure group, the additive and recessive models of rs293796 and the recessive model of rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05), while the dominant model of rs3219008 was protective factor of increasing urinary 8-OHdG level(P<0.05), after adjusting the potential influencing factors such as age, BMI, gender, smoking, drinking. However, after multiple Bonferroni correction tests, only the recessive model of rs293796 was the risk factor of increasing urinary 8-OHdG level in the exposed group(P<0.01). There was significant interaction between chromate exposure and rs293796 on urinary 8-OHdG(P<0.01). Conclusion The rs13096551 and rs293796 of hOGG1 were associated with the alteration of urinary 8-OHdG level induced by chromate. There was interaction between rs294796 of hOGG1 and chromate exposure on urinary 8-OHdG level.
Objective To evaluate the genetic damage induced by occupational chromate exposure, and to analyze the association between human 8-oxoguanine-DNA N-glycosylase 1(hOGG1) polymorphisms and genetic damage in population with chromate exposure. Methods A total of 136 chromate exposed workers were recruited as exposure group by judgmental sampling method, and 156 workers without chromate and other occupational hazard factors exposure were recruited as control group. The whole blood chromium(WB-Cr) level was measured by inductively coupled plasma mass spectrometry. Urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG) was determined by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms of hOGG1 gene were genotyped by the matrix assisted laser desorption ionization/time of flight mass spectrometry. Results The WB-Cr level was higher in the exposure group than that in the control group(meclian: 3.41 vs 0.90 μg/L, P<0.01). The urinary 8-OHdG level was higher in the exposure group compared with that in the control group(meclian: 6.02 vs 4.72 μg/g·creatinine, P<0.01). In study subjects(exposure group and control group), after adjusting the potential influencing factors such as age, body mass index(BMI), gender, smoking and drinking, chromate exposure might be a risk factor for increasing urinary 8-OHdG level(P<0.05), and the recessive models of rs293796 and rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05). In chromate exposure group, the additive and recessive models of rs293796 and the recessive model of rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05), while the dominant model of rs3219008 was protective factor of increasing urinary 8-OHdG level(P<0.05), after adjusting the potential influencing factors such as age, BMI, gender, smoking, drinking. However, after multiple Bonferroni correction tests, only the recessive model of rs293796 was the risk factor of increasing urinary 8-OHdG level in the exposed group(P<0.01). There was significant interaction between chromate exposure and rs293796 on urinary 8-OHdG(P<0.01). Conclusion The rs13096551 and rs293796 of hOGG1 were associated with the alteration of urinary 8-OHdG level induced by chromate. There was interaction between rs294796 of hOGG1 and chromate exposure on urinary 8-OHdG level.
引文
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[17] SIMONELLI V,CAMERINI S,MAZZEI F,et al.Genotype-phenotype analysis of S326C OGG1 polymorphism:a risk factor for oxidative pathologies[J].Free Radic BiolMed,2013,63:401-409.
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[19] WANG T,JIA G,ZHANG J,et al.Renal impairment caused by chronic occupational chromate exposure[J].Int Arch Occup Environ Health,2011,84(4):393-401.
[20] MYERS C R.The effects of chromium(Ⅵ) on the thioredoxin system:implications for redox regulation[J].Free Radic BiolMed,2012,52(10):2091-2107.
[21] WISE S S,ABOUEISSA A E,MARTINO J,et al.Hexavalent chromium-induced chromosome instability drives permanent and heritable numerical and structural changes and a DNA repair-deficient phenotype[J].Cancer Res,2018,78(15):4203-4214.
[22] SONG Y,ZHANG J,YU S,et al.Effects of chronic chromium(vi) exposure on blood element homeostasis:an epidemiological study [J].Metallomics,2012,4(5):463-472.
[23] 龚伟,吉俊敏,吴林林,等.某电镀企业工人低水平六价铬接触调查[J].中国职业医学,2018,45(2):235-238.
[24] LONG C,LIU J,HU G,et al.Modulation of homologous recombination repair gene polymorphisms on genetic damage in chromate exposed workers[J].Environ ToxicolPharmacol,2019,66:126-132.
[25] SMART D J,CHIPMAN J K,HODGES N J.Activity of OGG1 variants in the repair of pro-oxidant-induced 8-oxo-2’-deoxyguanosine[J].DNA Repair (Amst),2006,5(11):1337-1345.
[26] SMOLARZ B,MICHALSKA M M,SAMULAK D,et al.Studies of correlations between single nucleotide polymorphisms of DNA repair genes and endometrial cancer in Polish women[J].Anticancer Res,2018,38(9):5223-5229.
[27] SARLINOVA M,MAJEROVA L,MATAKOVA T,et al.Polymor-phisms of DNA repair genes and lung cancer in chromium exposure[J].Adv Exp Med Biol,2015,833:1-8.
[28] ZHANG X,ZHANG X,ZHANG L,et al.XRCC1 Arg399Gln was associated with repair capacity for DNA damage induced by occupational chromium exposure[J].BMC Res Notes,2012,5:263.
[29] JENSEN A,LOHR M,ERIKSEN L,et al.Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity[J].Free Radic Biol Med,2012,52(1):118-125.
[30] BAPTISTE B A,KATCHUR S R,FIVENSON E M,et al.Enhanced mitochondrial DNA repair of the common disease-associated variant,Ser326Cys,of hOGG1 through small molecule intervention[J].Free Radic Biol Med,2018,124:149-162.
[31] MOHAMED R H,EL-SHAL A S,EL-SHAHAWY E E,et al.Association of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in Egyptian patients[J].Gene,2016,578(1):112-116.
[2] 胡贵平,赵琳,刘佳兴,等.长期铬酸盐职业接触对人体外周血红细胞含量的影响[J].中华预防医学杂志,2017,51(1):41-46.
[3] HU G,ZHENG P,FENG H,et al.Imbalance of oxidative and reductive species involved in chromium (Ⅵ)-induced toxic effects[J].Reactive Oxygen Species,2017,7(3):1-11.
[4] LI P,LI Y,ZHANG J,et al.Establishment of a reference value for chromium in the blood for biological monitoring among occupational chromium workers[J].Toxicol Ind Health,2016,32(10):1737-1744.
[5] HU G,LI P,CUI X,et al.Cr(Ⅵ)-induced methylation and down-regulation of DNA repair genes and its association with markers of genetic damage in workers and 16HBE cells[J].Environ Pollut,2018,238:833-843.
[6] KUO H W,CHANG S F,WU K Y,et al.Chromium (Ⅵ) induced oxidative damage to DNA:increase of urinary 8-hydroxydeoxy-guanosine concentrations (8-ohdg) among electroplating workers [J].Occup Environ Med,2003,60(8):590-594.
[7] ALSAAD A M,AL-ARIFI M N,MAAYAH Z H,et al.Genotoxic impact of long-term cigarette and waterpipe smoking on DNA damage and oxidative stress in healthy subjects[J].Toxicol Mech Methods,2019,29(2):119-127.
[8] SINITSKY M Y,MININA V I,ASANOV M A,et al.Association of DNA repair gene polymorphisms with genotoxic stress in underground coal miners[J].Mutagenesis,2017,32(5):501-509.
[9] GENG P,YAO J,ZHU Y.hOGG1 Ser326Cys polymorphism and lung cancer susceptibility:a meta-analysis[J].Mol Biol Rep,2014,41(4):2299-2306.
[10] BORGHINI A,FAITA F,MERCURI A,et al.Arsenic exposure,genetic susceptibility and leukocyte telomere length in an Italian young adult population[J].Mutagenesis,2016,31(5):539-546.
[11] KANG S W,KIM S K,PARK H J,et al.Human 8-oxoguanine DNA glycosylase gene polymorphism (Ser326Cys) and cancer risk:updated meta-analysis[J].Oncotarget,2017,8(27):44761-44775.
[12] 杨晓颖,丁春光,闫慧芳.电感耦合等离子体-质谱法检测全血中铬[J].中国职业医学,2014,41(2):208-210.
[13] 李苹,李阳,张济,等.工作场所可溶性铬酸盐职业接触限值的探讨[J].中华预防医学杂志,2014,48(3):222-224.
[14] LI P,GU Y,YU S,et al.Assessing the suitability of 8-OHdG and micronuclei as genotoxic biomarkers in chromate-exposed workers:a cross-sectional study[J].BMJ Open,2014,4(10):e005979.
[15] MOHAMED R H,EL-SHAL A S,EL-SHAHAWY E E,et al.Association of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in Egyptian patients[J].Gene,2016,578(1):112-116.
[16] KERSHAW R M HODGES N J.Repair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1[J].Mutagenesis,2012,27(4):501-510.
[17] SIMONELLI V,CAMERINI S,MAZZEI F,et al.Genotype-phenotype analysis of S326C OGG1 polymorphism:a risk factor for oxidative pathologies[J].Free Radic BiolMed,2013,63:401-409.
[18] WILBUR S,ABADIN H,FAY M,et al.Toxicological profile for chromium[M].//Agency for toxic substances and disease registry (ATSDR) toxicological profiles.Atlanta (GA):Agencyfor Toxic Substances and Disease Registry (US):2012:13-56.
[19] WANG T,JIA G,ZHANG J,et al.Renal impairment caused by chronic occupational chromate exposure[J].Int Arch Occup Environ Health,2011,84(4):393-401.
[20] MYERS C R.The effects of chromium(Ⅵ) on the thioredoxin system:implications for redox regulation[J].Free Radic BiolMed,2012,52(10):2091-2107.
[21] WISE S S,ABOUEISSA A E,MARTINO J,et al.Hexavalent chromium-induced chromosome instability drives permanent and heritable numerical and structural changes and a DNA repair-deficient phenotype[J].Cancer Res,2018,78(15):4203-4214.
[22] SONG Y,ZHANG J,YU S,et al.Effects of chronic chromium(vi) exposure on blood element homeostasis:an epidemiological study [J].Metallomics,2012,4(5):463-472.
[23] 龚伟,吉俊敏,吴林林,等.某电镀企业工人低水平六价铬接触调查[J].中国职业医学,2018,45(2):235-238.
[24] LONG C,LIU J,HU G,et al.Modulation of homologous recombination repair gene polymorphisms on genetic damage in chromate exposed workers[J].Environ ToxicolPharmacol,2019,66:126-132.
[25] SMART D J,CHIPMAN J K,HODGES N J.Activity of OGG1 variants in the repair of pro-oxidant-induced 8-oxo-2’-deoxyguanosine[J].DNA Repair (Amst),2006,5(11):1337-1345.
[26] SMOLARZ B,MICHALSKA M M,SAMULAK D,et al.Studies of correlations between single nucleotide polymorphisms of DNA repair genes and endometrial cancer in Polish women[J].Anticancer Res,2018,38(9):5223-5229.
[27] SARLINOVA M,MAJEROVA L,MATAKOVA T,et al.Polymor-phisms of DNA repair genes and lung cancer in chromium exposure[J].Adv Exp Med Biol,2015,833:1-8.
[28] ZHANG X,ZHANG X,ZHANG L,et al.XRCC1 Arg399Gln was associated with repair capacity for DNA damage induced by occupational chromium exposure[J].BMC Res Notes,2012,5:263.
[29] JENSEN A,LOHR M,ERIKSEN L,et al.Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity[J].Free Radic Biol Med,2012,52(1):118-125.
[30] BAPTISTE B A,KATCHUR S R,FIVENSON E M,et al.Enhanced mitochondrial DNA repair of the common disease-associated variant,Ser326Cys,of hOGG1 through small molecule intervention[J].Free Radic Biol Med,2018,124:149-162.
[31] MOHAMED R H,EL-SHAL A S,EL-SHAHAWY E E,et al.Association of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in Egyptian patients[J].Gene,2016,578(1):112-116.