降钙素受体基因与氟性骨损伤相关因素的交互作用

Interaction of Calcitonin Receptor Gene and Fluoride Bone Injury Relevant Factors

[目的]分析与评价职业性氟接触人群降钙素受体基因（CTR）多态性及其与氟性骨损伤相关因素的交互作用,为氟性骨损伤干预政策及措施的制定提供理论依据。[方法]对湖北省某铝厂氟暴露工人245例进行流行病学调查和实验室检查,以右前臂和骨盆X射线正位片确定的氟性骨损伤119例作为病例组,其余126例作为对照组。检测病例组和对照组工人的CTR基因多态性、血氟（BF）、尿氟（UF）、血清骨钙素（BGP）、降钙素（CT）、碱性磷酸酶（ALP）和骨特异性碱性磷酸酶（BALP）等指标。[结果]氟暴露工人CTR基因型为CC型169例（69.0%）,TC型70例（28.6%）,TT型6例（2.4%）;C、T等位基因频率分别为83.3%和16.7%。影响氟性骨损伤发生的独立危险因素为饮酒,UF高、BGP高、CT高、BALP高及CTR基因型（非CC型）,其OR值分别为1.729,1.217,1.579,1.049,1.024和14.620。CTR T等位基因与UF存在正相加模型交互作用[交互作用超额相对危险度（RERI）=14.34（95%CI：1.47～32.16）,交互作用归因比（API）=0.75（95%CI：0.50～1.00）,交互作用指数（S）=4.7（95%CI：1.65～14.89）]。[结论]本次研究的结果显示饮酒,UF、BGP、CT、BALP高和CTR基因型（非CC型）是氟性骨损伤的危险因素,CTR T等位基因与UF在氟性骨损伤的发生中存在交互作用。

[ Objective ] To analyze the polymorphism of calcitonin receptor （CTR） gene in occupational fluoride exposure populations, assess its interaction with factors of fluoride bone injury, and provide a theoretical basis for the making of prevention strategies and measures of fluoride bone injury. [ Methods ] Our study included 245 workers exposed to fluoride at an aluminum plant in Hubei Province for epidemiological investigations and laboratory tests. Workers with fluoride bone injury （n=119） were determined by right forearm and pelvis anteroposterior x-ray films, and the rest workers （n=126） were set as controls. Measurements included CTR gene polymorphism, blood fluoride （BF）, urine fluoride （UF）, serum osteocalcin （BGP）, serum caleitonin （CT）, alkaline phosphatase （ALP）, and bone specific alkaline phosphatase （BALP）. [ Results ] The CTR genotypes of the fluoride exposed workers were CC （169 cases, 69.0%）, TC （70 cases, 28.6%）, and TT （6 cases, 2.4%）; the C and T allele frequencies were 83.3% and 16.7% respectively. Independent risk factors for fluoride bone injury were alcohol consumption, higher levels of UF, BGP, CT, BALP, and CTR gene （except CC genotype）, with the OR values of 1.729, 1.217, 1.579, 1.049, 1.024, and 14.620, respectively. The interaction between CTR T allele and UF was fit into a positive additive model [relative excess risk of interaction （RER/）=14.34 （95%CI： 1.47-32.16）, attributable proportion of interaction （AP/）=0.75 （95%CI： 0.50-1.00）, synergy index （S）=4.7 （95%CI： 1.65-14.89）]. [ Conclusion ] The study findings indicate that alcohol consumption, higher levels of UF, BGP, CT, BALP, and carrying CTR gene （except CC genotype） could be the risk factors of fluoride bone injury and CTR T allele is interacted with UF.