砷暴露多态变异与疾病易感性关联的生化调查

IF 5.3 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Emerging Contaminants Pub Date : 2024-07-20 DOI:10.1016/j.emcon.2024.100393

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引用次数: 0

摘要

我们的研究旨在确定多态性变异与砷诱发的代谢紊乱中疾病易感性之间的关联，这种疾病是由于接触饮用水中砷的人群中砷甲基化的变异性引起的。研究人员从巴基斯坦费萨拉巴德的不同地区系统地采集了水样，并通过电感耦合等离子体发射分光光度法（ICP-OES）对水样中的砷进行了定量分析。与费萨拉巴德供水和卫生机构（WASA）供应的水（9.81 ± 1.2 μg/L）和当地过滤的水（8.12 ± 1.42 μg/L）相比，地下水的砷浓度明显升高（68.18 ± 21.28 μg/L），经单向方差分析和 Bonferroni 后检验，P < 0.05。砷浓度与糖尿病等疾病的发病率之间存在关联。研究人员招募了居住在费萨拉巴德区六个地区的 120 名参与者。采集尿液和血液样本进行分析。利用锗作为内标，在氦碰撞模式下对尿液样本进行 ICP-MS 分析。收集的血液样本用于生物标志物评估，包括 HbA1c、BUN、肌酐、CRP、ALT、AST、GSH、SOD 和 MDA，以调查糖尿病的证据。结果发现，约 22.50% 的参与者尿砷浓度较高（P < 0.05），平均值为 68.43 ± 16.73 ppb。对这些参与者进行的生物标志物分析显示，其平均值分别为尿素氮（37.19 ± 2.87 mg/dL）、肌酐（2.58 ± 0.18 mg/dL）、IL-6（11.35 ± 6.98 pg/mL）、CRP（1.90 ± 0.26 mg/dL）、MDA（3.70 ± 0.18 nmol/mL）、谷丙转氨酶（40.27 ± 5.41 U/L）和谷草转氨酶（38.92 ± 4.72 U/L）。此外，基于性别的分析表明，使用 HPLC-ICP-MS 分析尿液样本时，男性的 DMA、MMA、TAs 和 TiAs 含量高于女性。GSTM 基因型为阳性的参与者尿液中的 TAs 和 TiAs 含量明显高于 GSTM 基因型为阴性的参与者。此外，与基因型为 GSTT1（-）和 GSTM1（-）的人相比，基因型为 GSTT1 和 GSTM1 阳性的人尿液中的 DMA 含量更高，但这一差异未达到统计学意义。与基因型为 GSTT1（-）的人相比，基因型为 GSTT1（+）的人显示出更高的二级甲基化指数。研究发现，MMA 和 DMA 的水平与 GSTT1 和 GSTM1 的基因型以及尿液中 TA 的含量有关。总之，我们的研究结果表明，砷甲基化（尤其是 DMA 和 SMI 水平）与 GSTT1 和 GSTM1 多态性之间存在联系。

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Biochemical investigation of association of arsenic exposed polymorphic variants and disease susceptibility

Our study aimed to establish the association of polymorphic variants and disease susceptibility in arsenic-induced metabolic disorders raised due to the variability of arsenic methylation in human population exposed to arsenic in drinking water. Water samples were systematically collected from various regions of Faisalabad, Pakistan, and subjected to arsenic quantification through inductively coupled plasma emission spectrophotometry (ICP-OES). The groundwater exhibited significantly elevated arsenic concentrations (68.18 ± 21.28 μg/L) in comparison to both water and sanitation agency Faisalabad (WASA)-supplied water (9.81 ± 1.2 μg/L) and locally filtered water (8.12 ± 1.42 μg/L), as determined by one-way ANOVA followed by Bonferroni's post-test at P < 0.05. An association was established between arsenic concentration and the incidence of disease, such as diabetes mellitus. A cohort of 120 participants residing in six areas of District Faisalabad was recruited. Urine and blood specimens were collected for analysis. Urine samples underwent ICP-MS analysis in helium collision mode, utilizing germanium as an internal standard. Blood samples were collected for biomarker assessments, including HbA1c, BUN, creatinine, CRP, ALT, AST, GSH, SOD, and MDA, to investigate the evidence of diabetes mellitus. Urinary arsenic concentrations were found to be considerably higher (P < 0.05) in about 22.50 % of the participants, with a mean value of 68.43 ± 16.73 ppb. Biomarker analysis in these participants revealed mean values for BUN (37.19 ± 2.87 mg/dL), creatinine (2.58 ± 0.18 mg/dL), IL-6 (11.35 ± 6.98 pg/mL), CRP (1.90 ± 0.26 mg/dL), MDA (3.70 ± 0.18 nmol/mL), ALT (40.27 ± 5.41 U/L), and AST (38.92 ± 4.72 U/L). Furthermore, the gender-based analysis indicated the higher levels of DMA, MMA, TAs, and TiAs in males compared to females when urine samples were analyzed with HPLC-ICP-MS. Participants with the positive genotype of GSTM exhibited significantly higher levels of TAs, and TiAs concentration in their urine than those with the null genotype of GSTM. Moreover, participants with positive genotypes for GSTT1 and GSTM1 demonstrated elevated levels of DMA in their urine compared to those with genotypes of GSTT1 (−) and GSTM1 (−), although this difference did not attain statistical significance. Participants with the genotype of GSTT1 (+) displayed a considerably higher secondary methylation index than those with genotype of GSTT1 (−). MMA and DMA levels were found to be correlated with the genotypes of GSTT1 and GSTM1 and the amounts of TAs in urine. In conclusion, our findings suggest a linkage between arsenic methylation, particularly levels of DMA and SMI, and GSTT1 and GSTM1 polymorphisms.

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来源期刊

Emerging Contaminants Medicine-Public Health, Environmental and Occupational Health

CiteScore

10.00

自引率

6.70%

发文量

审稿时长

44 days

期刊介绍： Emerging Contaminants is an outlet for world-leading research addressing problems associated with environmental contamination caused by emerging contaminants and their solutions. Emerging contaminants are defined as chemicals that are not currently (or have been only recently) regulated and about which there exist concerns regarding their impact on human or ecological health. Examples of emerging contaminants include disinfection by-products, pharmaceutical and personal care products, persistent organic chemicals, and mercury etc. as well as their degradation products. We encourage papers addressing science that facilitates greater understanding of the nature, extent, and impacts of the presence of emerging contaminants in the environment; technology that exploits original principles to reduce and control their environmental presence; as well as the development, implementation and efficacy of national and international policies to protect human health and the environment from emerging contaminants.