Kalahasthi Ravibabu, Adepu Vinay Kumar, Nagaraju Raju
Department of Biochemistry, Regional Occupational Health Centre (Southern), Indian Council of Medical Research, ICMR Complex, Kannamangala Post, Poojanahalli Road Devanahalli Taluk, Bengaluru, Karnataka 562110 India.
Indian J Clin Biochem. 2024 Oct;39(4):572-578. doi: 10.1007/s12291-023-01138-z. Epub 2023 Jun 12.
This study investigated the diagnostic accuracy (DA) and clinical utility (CU) of DNA methylation (5 methylcytosine) in occupational Pb-exposure from Pb based industry. Blood Lead levels (BLLs) were measured using the ICP-OES method. The total DNA methylation (5-mC) was quantified using ELISA method. Based on their BLLs, the Pb-exposed workers were categorised into three groups: low (< 10 µg/dL), moderate (10-30 µg/dL), and high exposure (> 30 µg/dL). DNA methylation (5-mC) was significantly lower in moderate and high Pb-exposure groups when compared to the low Pb-exposure group. Workers exposed to high levels of Pb-exposure, the DA variables of 5-mC showed that the sensitivity was 74.7% [95% CI 65.4-84.0], specificity was 69.6% [95% CI 50.8-88.4], positive predictive value (PPV) was 89.9% [95% CI 82.7-97.0], Postive likelihood ratio (LR+) was 2.454 [95% CI 1.3-4.6], and diagnostic odds ratio (DOR) is 6.3 [95% CI 6.5-7.7]. In moderate Pb-exposure, the DA variables of 5-mC revealed that the sensitivity is 64.9% [95% CI 55.2-74.5], the specificity is 69.6% [95% CI 50.8-88.4], the PPV is 89.7% [95% CI 82.5-97.0], the LR+ is 2.132 [95% CI 1.13-4.03], and the DOR is 4.2 [95% CI 3.6-5.7]. The high Pb-exposure group had higher DA metrics when compared to moderate Pb exposure. The clinical utility (CU+) of 5-mC was found to have good utility of 0.671 [95% CI 0.566-0.776] in the high Pb exposure group and fair utility of 0.582 [95% CI 0.470-0.694] in moderate Pb exposure group. In conclusion, DNA methylation (5mC) could be used as a predictive biomarker for high Pb-exposure.
本研究调查了基于铅的工业中职业性铅暴露的DNA甲基化（5-甲基胞嘧啶）的诊断准确性（DA）和临床效用（CU）。使用电感耦合等离子体发射光谱法（ICP-OES）测量血铅水平（BLLs）。采用酶联免疫吸附测定法（ELISA）对总DNA甲基化（5-mC）进行定量。根据血铅水平，将铅暴露工人分为三组：低暴露组（<10μg/dL）、中度暴露组（10 - 30μg/dL）和高暴露组（>30μg/dL）。与低铅暴露组相比，中度和高铅暴露组的DNA甲基化（5-mC）显著降低。在高铅暴露工人中，5-mC的诊断准确性变量显示，敏感性为74.7%[95%置信区间65.4 - 84.0]，特异性为69.6%[95%置信区间50.8 - 88.4]，阳性预测值（PPV）为89.9%[95%置信区间82.7 - 97.0]，阳性似然比（LR+）为2.454[95%置信区间1.3 - 4.6]，诊断比值比（DOR）为6.3[95%置信区间6.5 - 7.7]。在中度铅暴露中，5-mC的诊断准确性变量显示，敏感性为64.9%[95%置信区间55.2 - 74.5]，特异性为69.6%[95%置信区间50.8 - 88.4]，PPV为89.7%[95%置信区间82.5 - 97.0]，LR+为2.132[95%置信区间1.13 - 4.03]，DOR为4.2[95%置信区间3.6 - 5.7]。与中度铅暴露相比，高铅暴露组的诊断准确性指标更高。5-mC的临床效用（CU+）在高铅暴露组中具有良好效用，为0.671[95%置信区间0.566 - 0.776]，在中度铅暴露组中具有中等效用，为0.582[95%置信区间0.470 - 0.694]。总之，DNA甲基化（5mC）可作为高铅暴露的预测生物标志物。
