细胞色素氧化酶P4501A1基因rs1048943位点单核苷酸多态性与饮茶型氟中毒民族差异性的关系

Relationship between rs1048943 polymorphism of Cytochrome P-450 1A1 gene and the ethnic differences to brick-tea fluorosis

目的探讨细胞色素氧化酶P450（CYP）1A1基因多态性与饮茶型氟中毒民族差异性的关系以及基因．环境之间的交互作用。方法2012年，在内蒙古、青海和新疆的饮茶型氟中毒重点病区乡，对16岁以上人群进行问卷调查。内容包括基本信息、膳食调查和总氟摄入情况；同时采集外周静脉血，采用SequenomMassArray时间飞行质谱生物芯片系统对CYP1A1基因rs1048943位点单核苷酸多态性（SNP）分型进行检测；采用X线摄片法对氟骨症进行诊断；比较CYP1A1基因rs1048943位点基因型分布的民族差异性．并结合环境因素进行单因素Logistic回归分析。结果共有1414名受试者入选，其中藏族308人、哈萨克族290人、蒙古族261人、汉族425人、俄罗斯族130人。受试者全血的CYP1A1基因rs1048943位点的基因型分为AA、AG、GG3种，藏族基因型分布频率分别为55．8％（172／308）、37.3％（115／308）、6．8％（21／308）；哈萨克族分别为69．7％（202／290）、27．6％（80／290）、2．8％（8／290）；蒙古族分别为60．5％（158／261）、36．0％（94／261）、3．4％（9／261）；汉族分别为60．9％（259／425）、33．6％（143／425）、5．4％（23／425）；俄罗斯族分别为72．3％（94／130）、26．9％（35／130）、0．8％（1／130），经Hardy．Weinberg遗传平衡定律检验，5个民族CYP1A1基因rs1048943位点的基因型多态性均符合遗传平衡定律（P均〉0．05）；不同民族之间CYP1A1基因rs1048943位点基因型分布不同（X2=24．757，P〈0．05）。不同民族氟骨症检出率从高到低依次为藏族（39．94％，123／308）、哈萨克族（33．79％，98／290）、蒙古族（22．22％，58／261）、汉族（13．41％，57／425）和俄罗斯族（8．46％，11／130），民族间差异有统计学意义（Х^2=100．156，P〈0．05）。将CYP1A1基因rs1048943位点AG与GG基因型合并后（AG／GG）氟骨症检出率（25．14％，133／529）与AA（24．18％，214／885）比较，差异无统计学意义（Х^2=0．165，P〉0．05）。按民族分层后，各民族CYPIAl基因多态性与氟骨症检出率间未见相关性（P均〉0．05）。单因素Logistic回归分析显示，仅在尿氟水平为1．6～3．2ms／L的藏族人群以及蒙古族〈45岁人群中，发现G基因是饮茶型氟中毒氟骨症的危险因素[OR=2．035，95％CI（1．003～4．128）；OR=5．602，95％CI（1．461～21．479）]；在蒙古族I〉45岁人群中G基因是保护因素[OR=0．422，95％CI（0．190．0．938）]。结论CYP1A1基因rs1048943位点多态性与饮茶型氟中毒民族差异性无关。

Objective To investigate the relationship between Cytochrome P-450 1A1 （CYP1A1） gene polymorphism and the ethnic differences to brick-tea fluorosis and the gene-environment interaction. Methods Inhabitants over the age of 16 years old in Inner Mongolia, Qinghai and Xinjiang were investigated. The questionnaire survey included basic information, dietary survey and total fluoride intake, and peripheral venous blood was collected. The CYP1A1 gene single nucleotide polymorphism （SNP） genotyping was determined using mass spectrometry; the diagnosis of skeletal fluorosis was based on the X-ray method; combined genetic factors with environmental factors, the interaction of gene-environment was analyzed. Results In the 1 414 copies of whole blood samples （308 Tibetans, 290 Kazakhs, 261 Mongolians, 425 Han people, 130 Russians）, CYP1A1 genes rs1048943 sites were typed into AA, AG and GG genotypes, and gene distribution met Hardy-Weinberg equilibrium （P 〉 0.05）. The frequencies of genotypes AA, AG and GG in Tibetans were 55.8% （172/308）, 37.3% （115/308） and 6.8% （21/308）, respectively; the frequencies of the three genotypes in Kazakhs were 69.7% （202/290）, 27.6% （80/290） and 2.8% （8/ 290）, respectively; the frequencies of the three genotypes in Mongolians were 60.5% （158/261）, 36.0% （941261） and 3.4% （9/261）, respectively;, the frequencies of the three genotypes in Han people were 60.9% （259/425）, 33.6% （143/ 425） and 5.4% （23/425）, respectively; the frequencies of genotypes in Russians were 72.3% （94/130）, 26.9% （35/ 130） and 0.8% （1/130）, respectively;, the differences of the three genotype frequencies between different ethnic groups were statistically significant （Х^2 = 24.757, P 〈 0.05）. The skeletal fluorosis detection rates in different ethnic from high to low were Tibetans （39.94%, 123/308）, Kazakhs （33.79%, 98/290）, Mongolians （22.22%, 58/261）, Han people （13.41%, 57/425） and Russians （8.46%, 11/130）, and the differences were statistically significant （Х^2 = 100.156, P 〈 0.05）. Skeletal fluorosis detection rates of different genotypes were AA （24.18%, 214/885）, AG/GG （25.14%, 133/529）, the difference was not statistically significant between the groups （Х^2 = 0.165, P 〉 0.05）. After the ethnic stratification, the differences were also not statistically significant （P 〉 0.05）. Only in the group of Tibetans whose urine fluoride level was 1.6 - 3.2 mg/L and Mongolians under age 45 were found that the G gene was one of the risk factors in skeletal fluorosis [OR = 2.035, 95% CI （1.003 - 4.128）; OR = 5.602, 95%CI （1.461- 21.479）]; G gene might be a protective factor in the Mongolians aged 45 years and over [OR = 0.422,95%CI（0.190 - 0.938）]. Conehtsion This study does not find a positive correlation between CYP1A1 gene polymorphism and the ethnic differences to bricktea fluorosls.