FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China
FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China
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FRZB1 rs2242070 多态性与哈萨克人的砖茶型氟骨症有关，但与中国藏人无关
DOI：
10.1007/s00204-018-2217-9
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发表时间：
2018-07-01
影响因子：
6.1
通讯作者：
Gao，Yanhui
中科院分区：
文献类型：
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作者：
Yang，Yanmei;Zhao，Qiaoshi;Gao，Yanhui
氟骨症是由于氟化物在骨骼中蓄积过多而引起的一种代谢性骨关节疾病。与哈萨克族相比，藏族人虽然氟暴露水平相似，但更容易患中度和重度砖茶型氟骨症。卷曲相关蛋白 (FRZB) 中的单核苷酸多态性 (SNP) 与骨关节炎相关，但其与氟骨症风险的关联尚未见报道。在本文中，我们在中国新疆和青海进行的横断面病例对照研究中调查了 FRZB1 中的三个 SNP（rs7775、rs2242070 和 rs9288087）与砖茶型氟骨症风险的关联。本研究共纳入 598 人，其中藏族 308 人、哈萨克人 290 人，其中病例 221 例、对照 377 例。氟骨症诊断按照中国地方性氟骨症诊断标准（WS192-2008）。采用氟离子电极检测茶水或尿液中的氟含量。使用 Sequenom MassARRAY 系统评估 SNP。二元 Logistic 回归仅在哈萨克族参与者中发现与 rs2242070 AA 基因型相关的证据 [比值比 (OR) 0.417, 95% CI 0.216–0.807,p= 0.009]，但在藏族中则不然。按年龄分层时，rs2242070 中 AA 基因型的这种保护作用在 46-65 岁的哈萨克参与者中很明显（OR 0.321，95% CI 0.135-0.764，p= 0.010）。哈萨克人 rs2242070 中 AA 基因型的这种保护性关联似乎在茶氟化物摄入量 > 3.5 mg/天时更强（OR 0.396，95% CI 0.182–0.864，p= 0.020）。我们的数据表明，哈萨克族和藏族参与者的氟骨症风险可能存在不同的遗传影响，并且这种差异可能会通过茶氟化物的摄入而改变。
Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluorosis risk in a cross-sectional case–control study conducted in Sinkiang and Qinghai, China. A total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled in this study, in which cases and controls were 221 and 377, respectively. The skeletal fluorosis was diagnosed according to the Chinese diagnostic criteria of endemic skeletal fluorosis (WS192-2008). The fluoride content in tea water or urine was detected using the fluoride ion electrode. SNPs were assessed using the Sequenom MassARRAY system. Binary logistic regressions found evidence of association with rs2242070 AA genotype in only Kazakh participants [odds ratio (OR) 0.417, 95% CI 0.216–0.807,p= 0.009], but not in Tibetans. When stratified by age, this protective effect of AA genotype in rs2242070 was pronounced in Kazakh participants aged 46–65 (OR 0.321, 95% CI 0.135–0.764,p= 0.010). This protective association with AA genotype in rs2242070 in Kazakhs also appeared to be stronger with tea fluoride intake > 3.5 mg/day (OR 0.396, 95% CI 0.182–0.864,p= 0.020). Our data suggest there might be differential genetic influence on skeletal fluorosis risk in Kazakh and Tibetan participants and that this difference might be modified by tea fluoride intake.