钙敏感受体基因Rs1801726位点单核苷酸多态性与氟骨症的关系

Relationship between Rs1801726 polymorphism of calcium sensing receptor gene and skeletal fluorosis

目的探讨钙敏感受体（CaSR）基因Rs1801726位点单核苷酸多态性与氟骨症的关系。方法2012—2013年，在青海省果洛藏族自治州藏族，内蒙古自治区呼伦贝尔市蒙古族、俄罗斯族，新疆维吾尔自治区阿勒泰地区哈萨克族居住地区选择典型饮茶型氟中毒病区，每个地区选取2个县，并将每个县人口相对集中的3～4个饮茶型氟中毒病区乡确定为调查点。选取经现场X线诊断为氟骨症患者的347人为氟骨症组，非氟骨症患者1067人为非氟骨症组。藏族、哈萨克族、蒙古族、汉族、俄罗斯族分别为308、290、261、425、130人。对调查对象进行问卷调查，内容包括一般情况、日均砖茶水摄入量；采集5ml静脉血，采用质谱法检测CaSR基因Rsl801726位点单核苷酸多态性；采集砖茶水、尿样进行氟含量测定。砖茶氟和尿氟的测定采用离子选择电极法（wS／T89．2006）；使用便携式数字化X光机（DR）对调查对象的前臂、腰椎及盆骨进行X线拍片．x线氟骨症诊断依据《地方性氟骨症诊断标准》（WS／T192．2007），并结合流行病学特征及临床表现。结果经Hardy—Weinberg平衡检验，CaSR基因Rsl801726位点基因型在氟骨症、非氟骨症组及不同民族中均具有代表性（P均〉0．05）。氟骨症和非氟骨症组CaSR基因Rsl801726位点基因型（CC、CG）经二元Logistic回归分析，差异无统计学意义[粗比值比（OR）值为0．919（0．509～1．658）、调整OR值为0．979（0．521～1．840）]。不同民族氟骨症和非氟骨症组CasR基因Rsl801726位点基因型（CC、CG）经二元Logistic回归分析，差异无统计学意义[藏族：粗OR值为1．512（0．210～10．882）、调整OR值为1．700（0．224-12．908）；哈萨克族：粗OR值为1．517（0．616～3．734）、调整OR值为1．444（0．568～3．671）；蒙古族：粗OR值为1．000（0．202—4．949）、调整OR值为1．036（0．189～5．671）；汉族：粗OR值为0．369（0．048～2．825）、调整OR值为0．301（0．036—2．551）；俄罗斯族：粗OR值为0．892（0．105～7．582）、调整OR值为0．555（0．060—5．098）]。结论本研究未发现CaSR基因Rsl801726位点单核苷酸多态性在饮茶型氟中毒地区不同民族居民中存在差异。

Objective To investigate the relationship between single nucleotide polymorphism of the calcium sensing receptor gene （CaSR） Rs1801726 and skeletal fluorosis. Methods From 2012 to 2013, the Tibetan living area in Guoluo of Qinghai Province, the Mongolian, Russian living area in Hulun Buir City of the Inner Mongolia Autonomous Region and the Kazakh living area in Altay of Xinjiang Uygur Autonomous Region, two counties were chosen in each area and 3 to 4 drinking brick-tea type fluorosis districts were chosen as the investigated districts in the counties. Totally 347 patients with skeletal fluorosis diagnosed by X-ray were selected as skeletal fluorosis group, 1 067 people without skeletal fluorosis as non skeletal fluorosis group. Tibean, Kazak, Mongolia, Han, Russian were 308, 290, 261, 425, 130 people, respectively. A questionnaire survey of endemic fluorosis was conducted, the survey contents included general characteristics, average daily brick tea intake; 5 ml venous blood was collected, the single nucleotide polymorphism of Rs1801726 was detected by mass spectrometry; drinking water, brick tea and urine samples were collected and analyzed; forearm, lumbar spine and pelvis of subjects were examined by Portable DR. Water fluoride, brick tea fluorine and urinary fluoride were detected by ion selective electrode （WS/T 89-2006）. X-ray diagnosis of skeletal fluorosis was based on ＂Endemic Skeletal Fluorosis Diagnostic Criteria （WS/T 192-2007）, and epidemiological and clinical descriptive information were combined. Results By the Hardy-Weinberg balance test, the CaSR Rs1801726 gene loci genotype was representative in the group of skeletal fluorosis, the group of non skeletal fluorosis and each nationality （all P 〉 0.05）. The difference of CaSR gene Rs1801726 genotype （CC, CG） in the group of skeletal fluorosis and the group of non skeletal fluorosis was not statistically significant [crude OR value was 0.919 （0.509 - 1.658） and the adjusted OR value was 0.979 （0.521 - 1.840）] with binary Logistic regression analysis. The difference of CaSR gene Rs1801726 genotype （CC, CG） in the group of skeletal fluorosis and the group of non skeletal fluorosis in different nationality was not statistically significant [Tibetan： crude OR value was 1.512 （0.210 - 10.882） and the adjusted OR value was 1.700 （0.224 - 12.908）; Kazak： crude OR value was 1.517 （0.616 - 3.734） and the adjusted OR value was 1.444 （0.568 - 3.671）; Mongolia： crude OR value was 1.000 （0.202 - 4.949） and the adjusted OR value was 1.036 （0.189 - 5.671）; Ham crude OR value was 0.369 （0.048 - 2.825） and the adjusted OR value was 0.301 （0.036 - 2.551）; Russian： crude OR value was 0.892 （0.105 - 7.582） and the adjusted OR value was 0.555 （0.060 - 5.098）] with binary Logistic regression analysis. Corlelusion In this study, the polymorphism of CaSR Rs1801726 single nucleotide polymorphism is not related to the prevalence of fluorosis in different ethnic groups in our country.