Thurston Arthritis Research Center, Department of Radiology, University of North Carolina, 3300 Thurston Bldg, Chapel Hill, NC 27599, USA.
Environ Res. 2011 Nov;111(8):1208-14. doi: 10.1016/j.envres.2011.08.002. Epub 2011 Aug 12.
To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology.
Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-Study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level.
The median Pb level among men and women was 2.2 and 1.9μg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95% CI: 1.04-1.58], uNTX-I: 1.45 [95% CI:1.21-1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00-1.18]); no other associations were significant after adjustment.
Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships to bone and calcified cartilage turnover among women and cartilage metabolism among men, suggesting a potential gender-specific effect of Pb on joint tissue metabolism that may be relevant to osteoarthritis.
分别在非裔美国人和白种人群体中，研究关节组织代谢生物标志物与全血铅（Pb）之间的关联，这可能反映了潜在的病理情况。
参与约翰斯顿县骨关节炎项目金属暴露子研究（329 名男性和 342 名女性）的参与者接受了全血 Pb 和关节组织代谢生物标志物的评估。使用商业试剂盒测量尿型 I 胶原交联 N 末端肽（uNTX-I）和型 II 胶原 C 末端肽片段（uCTX-II）、血清 II 型胶原裂解新表位（C2C）、血清 II 型前胶原合成 C 前肽（CPII）和血清透明质酸（HA）；计算 [C2C:CPII] 的比值。血清软骨寡聚基质蛋白（COMP）通过内部测定法进行测量。使用多元线性回归模型，在调整年龄、种族、当前吸烟状况和体重指数后，研究连续血 Pb 与生物标志物结果之间的关联。结果以 Pb 水平每增加 5 个单位时生物标志物水平的估计变化来表示。
男性和女性的中位 Pb 水平分别为 2.2 和 1.9μg/dL。在女性中，Pb 水平与 uNTX-I、uCTX-II 和 COMP 标志物之间存在相关性，在男性中，Pb 水平与 uCTX-II、COMP、CPII 和 [C2C:CPII] 比值之间存在相关性。在女性的调整模型中，全血 Pb 水平每增加 5 个单位，uCTX-II 水平增加 28%，uNTX-I 水平增加 45%（uCTX-II：1.28[95%CI：1.04-1.58]，uNTX-I：1.45[95%CI：1.21-1.74]）。在男性中，Pb 和 COMP 水平呈正相关（Pb 每变化 5 个单位，COMP 水平增加 8%：1.08[95%CI：1.00-1.18]）；调整后，其他关联无统计学意义。
根据已知的生物标志物来源，血液 Pb 与生物标志物之间的新关联主要反映了女性骨骼和钙化软骨转化以及男性软骨代谢之间的关系，这表明 Pb 对关节组织代谢可能存在潜在的性别特异性影响，这与骨关节炎有关。
