环境低砷暴露地区2型糖尿病人群尿砷水平与外周血单个核细胞相对端粒长度的关系研究

doi:10.3969/j.issn.1004-616x.2023.02.008

癌变·畸变·突变 ›› 2023, Vol. 35 ›› Issue (2): 125-130,147.doi: 10.3969/j.issn.1004-616x.2023.02.008

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环境低砷暴露地区2型糖尿病人群尿砷水平与外周血单个核细胞相对端粒长度的关系研究

李洪娅¹, 廖清华², 付浩祥², 肖柏香³, 苏珩¹, 谢易容¹, 刘洁仪¹, 魏青¹, 王凤¹, 皮姝荣¹, 陈福彬¹, 赵志强⁴, 何云¹

1. 中山大学公共卫生学院毒理学教研室, 广东广州 510080;
2. 广东韶州人民医院, 广东韶关 512000;
3. 南昌大学附属眼科医院, 江西南昌 330006;
4. 广东省职业病防治院毒理实验所, 广东广州 510080

收稿日期:2023-01-14 修回日期:2023-02-28 发布日期:2023-04-13
通讯作者: 赵志强;何云
作者简介:李洪娅,E-mail：lihy68@mail2.sysu.edu.cn;廖清华,E-mail：sgtylqh@163.com。
基金资助:
国家自然科学基金（81872661，81472998）

Relationships between urine arsenic levels and relative telomere length in blood mononuclear cells among type-2 diabetic patients exposed to low levels of arsenic

LI Hongya¹, LIAO Qinghua², FU Haoxiang², XIAO Baixiang³, SU Heng¹, XIE Yirong¹, LIU Jieyi¹, WEI Qing¹, WANG Feng¹, PI Shurong¹, CHEN Fubin¹, ZHAO Zhiqiang⁴, HE Yun¹

1. Department of Health Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, Guangdong;
2. Guangdong Shaozhou People,s Hospital, Shaoguan 512000, Guangdong;
3. Affiliated Eye Hospital of Nanchang University, Nanchang 330006, Jiangxi;
4. Institute of Toxicology, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510080, Guangdong, China

Received:2023-01-14 Revised:2023-02-28 Published:2023-04-13

摘要/Abstract

摘要： 目的：探讨环境低砷暴露地区2型糖尿病人群尿砷浓度与外周血单个核细胞(PBMC)相对端粒长度的关系。方法：选取华南某地574名2型糖尿病患者作为研究对象，进行基本情况调查与生化指标检测，利用电感耦合等离子质谱仪(ICP-MS)检测尿砷浓度，实时荧光定量PCR法(qPCR)检测PBMC相对端粒长度。根据尿砷浓度将研究对象分为3组，比较各组间生化指标与PBMC相对端粒长度的差异；采用单因素与多因素有序 Logistic 回归分析研究 2 型糖尿病人群 PBMC 相对端粒长度的影响因素；采用 SPSSProcess 2.0分析糖化血红蛋白在尿砷与相对端粒长度之间的中介效应。结果：2型糖尿病患者尿砷中位数为29.80 μg/L，四分位数间距为39.81 μg/L。PBMC相对端粒长度为0.82±0.60，低砷组、中砷组与高砷组PBMC相对端粒长度分别为1.04±0.92，0.77±0.29与0.63±0.28，差异具有统计学意义(P<0.05)。多因素有序Logistic回归分析发现，尿砷是影响相对端粒长度的危险因素；中砷组与低砷组相比，OR(95% CI)为2.149(1.451，3.182)；高砷组与低砷组相比，OR(95% CI)为4.077(2.687，6.185)，差异均具有统计学意义(P<0.01)。中介效应分析结果显示，尿砷对相对端粒长度的直接效应值为-0.287(-0.369，-0.204)，糖化血红蛋白是尿砷与相对端粒长度之间的一个中介变量，中介效应值为-0.072(-0.106，-0.045)，中介比例为19.99%。结论：环境低砷暴露条件下，尿砷是影响2型糖尿病患者PBMC相对端粒长度的危险因素，尿砷浓度越高，相对端粒长度越短。2型糖尿病患者PBMC相对端粒长度可能是砷暴露的潜在生物标志。

关键词: 相对端粒长度, 尿砷, 2型糖尿病, 低水平砷暴露

Abstract: OBJECTIVE： To explore relationships between the relative telomere length of blood mononuclear cells (PBMC) and urine arsenic concentration in type-2 diabetic patients exposed to low levels of arsenic. METHODS：A total of 574 patients with type 2 diabetes in South China were selected as the study objects. Basic information was collected and biochemical indicators were detected. Urine arsenic concentrations were detected using inductively coupled plasma mass spectrometer (ICP-MS) technology，and relative telomere lengths of PBMC were detected by real-time fluorescence quantitative PCR (qPCR) technology. The study subjects were divided into 3 groups according to their urine arsenic concentrations. Differences of biochemical indicators and PBMC relative telomere lengths among the 3 groups were compared. Single-and multi-factor ordinal logistic regressions were used to analyze influencing factors for the relative telomere lengths. The mediating effects of Hemoglobin A_1c (HbA_1c) between urine arsenic levels and relative telomere lengths were analyzed using SPSS Process 2.0. RESULTS：The median urine arsenic level in the patients was 29.80 μg/L， and the interquartile interval was 39.81 μg/L，and the relative telomere length was 0.82±0.60. The relative telomere length in low， medium and high arsenic groups were 1.04 ±0.92， 0.77±0.29 and 0.63±0.28， respectively. Differences of relative telomere lengths among the three groups were statistically significant (P<0.05). Multivariate ordinal logistic regression analyses showed that urine arsenic was a risk factor for relative telomere length. Compared with the low arsenic group，the OR (95% CI) of the medium arsenic group was 2.149 (1.451， 3.182)， and that of the high arsenic group was 4.077 (2.687， 6.185)， the differences were statistically significant (P<0.01). The direct effect value of urine arsenic on relative telomere length was -0.287 (-0.369，-0.204). HbA_1c was a mediating variable between urine arsenic and relative telomere length，with the mediating effect value being -0.072 (-0.106，-0.045) and the mediating proportion being 19.99%. CONCLUSION：Presence of arsenic in urine is a risk factor for relative telomere length of PBMC in type-2 diabetic patients： the higher the urine arsenic levels，the shorter the relative telomere lengths. The relative telomere length of PBMC in these patients may be a potential biomarker for arsenic exposures.

Key words: relative telomere length, urine arsenic, type 2 diabetes, low level arsenic exposure

中图分类号:

R587.1

李洪娅, 廖清华, 付浩祥, 肖柏香, 苏珩, 谢易容, 刘洁仪, 魏青, 王凤, 皮姝荣, 陈福彬, 赵志强, 何云. 环境低砷暴露地区2型糖尿病人群尿砷水平与外周血单个核细胞相对端粒长度的关系研究[J]. 癌变·畸变·突变, 2023, 35(2): 125-130,147.

LI Hongya, LIAO Qinghua, FU Haoxiang, XIAO Baixiang, SU Heng, XIE Yirong, LIU Jieyi, WEI Qing, WANG Feng, PI Shurong, CHEN Fubin, ZHAO Zhiqiang, HE Yun. Relationships between urine arsenic levels and relative telomere length in blood mononuclear cells among type-2 diabetic patients exposed to low levels of arsenic[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(2): 125-130,147.

参考文献

[1] SHAY J W. Telomeres and aging[J]. Curr Opin Cell Biol, 2018, 52: 1-7.
[2] SERRA V, GRUNE T, SITTE N, et al. Telomere length as a marker of oxidative stress in primary human fibroblast cultures [J]. Ann N Y Acad Sci, 2000, 908: 327-330.
[3] VON ZGLINICKI T. Oxidative stress shortens telomeres[J]. Trends Biochem Sci, 2002, 27(7): 339-344.
[4] SHEN Q, ZHAO X Z, YU L, et al. Association of leukocyte telomere length with type 2 diabetes in mainland Chinese populations[J]. J Clin Endocrinol Metab, 2012, 97(4): 1371-1374.
[5] TESTA R, OLIVIERI F, SIROLLA C, et al. Leukocyte telomere length is associated with complications of type 2 diabetes mellitus[J]. Diabet Med, 2011, 28(11): 1388-1394.
[6] ZEE R Y, CASTONGUAY A J, BARTON N S, et al. Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study[J]. Transl Res, 2010, 155(4): 166-169.
[7] KONONENKO M, FRISHMAN W H. Association between arsenic exposure and cardiovascular disease[J]. Cardiol Rev, 2021, 29(4): 217-221.
[8] JOMOVA K, JENISOVA Z, FESZTEROVA M, et al. Arsenic: toxicity, oxidative stress and human disease[J]. J Appl Toxicol, 2011, 31(2): 95-107.
[9] GAO J J, ROY S, TONG L, et al. Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals[J]. Environ Res, 2015, 136: 462-469.
[10] CHATTERJEE D, BHATTACHARJEE P, SAU T J, et al. Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: a case-control study in West Bengal, India[J]. Mol Carcinog, 2015, 54(9): 800-809.
[11] LI H Q, ENGSTRÖM K, VAHTER M, et al. Arsenic exposure through drinking water is associated with longer telomeres in peripheral blood[J]. Chem Res Toxicol, 2012, 25(11): 2333-2339.
[12] FILLMAN T, SHIMIZU-FURUSAWA H, NG C F S, et al. Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal[J]. Environ Res, 2016, 149: 8-14.
[13] 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.
[14] RAHAMAN M S, RAHMAN M M, MISE N, et al. Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism and management[J]. Environ Pollut, 2021, 289: 117940.
[15] 刘少华, 章海宁, 陈爱萍, 等. 韶关市正常人群尿砷的正常参考值分析研究[J]. 中国医药科学, 2016, 6(19): 116-118, 145.
[16] 丁春光, 潘亚娟, 张爱华, 等. 中国八省份一般人群血和尿液中砷水平及影响因素调查[J]. 中华预防医学杂志, 2014, 48(2): 97-101.
[17] FARKHONDEH T, SAMARGHANDIAN S, AZIMI-NEZHAD M. The role of arsenic in obesity and diabetes[J]. J Cell Physiol, 2019, 234(8): 12516-12529.
[18] GAVIA-GARCÍA G, ROSADO-PÉREZ J, ARISTA-UGALDE T L, et al. Telomere length and oxidative stress and its relation with metabolic syndrome components in the aging[J]. Biology (Basel), 2021, 10(4): 253.
[19] HOU L F, ZHANG X, GAWRON A J, et al. Surrogate tissue telomere length and cancer risk: shorter or Longer?[J]. Cancer Lett, 2012, 319(2): 130-135.
[20] FITZPATRICK A L, KRONMAL R A, GARDNER J P, et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study[J]. Am J Epidemiol, 2007, 165(1): 14-21.
[21] ZHANG X, LIN S, FUNK W E, et al. Environmental and occupational exposure to chemicals and telomere length in human studies[J]. Occup Environ Med, 2013, 70(10): 743-749.
[22] MENKE A, CASAGRANDE S, COWIE C C. Leukocyte telomere length and diabetes status, duration, and control: the 1999-2002 National Health and Nutrition Examination Survey [J]. BMC Endocr Disord, 2015, 15: 52.
[23] HUG N, LINGNER J. Telomere length homeostasis[J]. Chromosoma, 2006, 115(6): 413-425.
[24] RIZVI S, RAZA S T, MAHDI F. Telomere length variations in aging and age-related diseases[J]. Curr Aging Sci, 2014, 7(3): 161-167.
[25] AVIV A. Genetics of leukocyte telomere length and its role in atherosclerosis[J]. Mutat Res, 2012, 730(1/2): 68-74.
[26] DONATO A J, MORGAN R G, WALKER A E, et al. Cellular and molecular biology of aging endothelial cells[J]. J Mol Cell Cardiol, 2015, 89: 122-135.
[27] TELLECHEA M L, PIROLA C J. The impact of hypertension on leukocyte telomere length: a systematic review and metaanalysis of human studies[J]. J Hum Hypertens, 2017, 31(2): 99-105.
[28] GRUNNET L G, PILGAARD K, ALIBEGOVIC A, et al. Leukocyte telomere length is associated with elevated plasma glucose and HbA1c in young healthy men independent of birth weight[J]. Sci Rep, 2019, 9(1): 7639.
[29] TAMURA Y, IZUMIYAMA-SHIMOMURA N, KIMBARA Y, et al. β-cell telomere attrition in diabetes: inverse correlation between HbA1c and telomere length[J]. J Clin Endocrinol Metab, 2014, 99(8): 2771-2777.
[30] 肖琛, 翁帆, 刘洁仪, 等. 低水平砷暴露的2型糖尿病患者尿砷与糖化血红蛋白的关系[J]. 癌变·畸变·突变, 2020, 32(2): 87-91, 97.

环境低砷暴露地区2型糖尿病人群尿砷水平与外周血单个核细胞相对端粒长度的关系研究

Relationships between urine arsenic levels and relative telomere length in blood mononuclear cells among type-2 diabetic patients exposed to low levels of arsenic

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