Genetic variation in the CYP2B6 gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study.
Genetic variation in the CYP2B6 gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study.
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DOI：
10.1186/1476-069x-13-34
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发表时间：
2014-05-08
期刊：
影响因子：
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通讯作者：
Lind PM
中科院分区：
文献类型：
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作者：
Penell J;Lind L;Fall T;Syvänen AC;Axelsson T;Lundmark P;Morris AP;Lindgren C;Mahajan A;Salihovic S;van Bavel B;Ingelsson E;Lind PM
由于人类CYP 2B 6已被确定为参与2，2 '，4，4'-四溴二苯醚（BDE-47）代谢的主要代谢酶，并且人类2B 6是一种高度多态的代谢酶，具有已知的功能变体，因此我们评估了主要溴化阻燃剂BDE-47的循环浓度是否与人群样本中CYP 2B 6基因的遗传变异有关。在基于人群的乌普萨拉老年人血管系统前瞻性研究（PIVUS）研究（年龄均为70岁的男性和女性）中，对CYP 2B 6基因的25个单核苷酸多态性（SNP）进行了基因分型。采用高分辨率气相色谱-高分辨率质谱联用技术（HRGC/ HRMS）分析了BDE-47的循环浓度。CYP 2B 6基因中的几个SNP与BDE-47的循环浓度相关（P = 10-4至10-9）。研究的SNPs主要来自两个单倍型，尽管单倍型之间的相关性相当高。调整与暴露（rs 2014141）相关性最强的SNP的条件分析未提供独立信号的证据。在老年人群中，BDE-47的循环浓度与CYP 2B 6基因的遗传变异有关。
Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10-4 to 10-9). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals. Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.