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乙醛脱氢酶2和细胞色素P4502E1基因多态性与甲醛职业危害易感性的关系

Relationship between susceptibility of formaldehyde metabolism and genetic polymorphisms of ALDH2 and cytochrome P4502E1
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摘要 目的探讨乙醛脱氢酶2(ALDH2)和细胞色素P4502E1(CYP2E1)基因多态性与甲醛职业危害易感性的关系。方法以107例甲醛接触者外周血淋巴细胞为样本,采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)方法测定ALDH2和CYP2E1(RsaⅠ/PstⅠ位点)基因型,高效液相色谱法(HPLC)检测空气中甲醛浓度和尿中甲酸含量,多组资料秩和检验分析不同ALDH2和CYP2E1基因型与甲醛接触者班末尿中代谢产物甲酸含量的关系。结果不同ALDH2基因型影响了尿中甲酸含量,野生纯合子(GG)、杂合子(GA)、突变纯合子(AA)型个体尿中甲酸平均含量分别为(15.84±6.86)、(12.06±7.94)、(7.31±5.37)mg/g肌酐,差异有统计学意义(χ^2=9.241,P〈0.05),AA和GG两组比较差异有统计学意义(U=26.00,P=0.033)。CYP2E1基因5′-空白区域RsaⅠ/PstⅠ位点多态性未影响尿中甲酸的含量,C1/C1、C1/C2、C2/C2型个体尿中甲酸平均浓度分别为:(11.14±7.91)、(12.13±8.16)、(16.51±3.78)mg/g肌酐,差异无统计学意义(χ^2=4.285,P=0.117)。多元回归分析变量为甲醛接触量和ALDH2基因型,模型的调整R^2=0.196。结论ALDH2外显子12上(G-A位点)多态性与人体内甲醛代谢易感性相关,而CYP2E1(RsaⅠ/PstⅠ位点)基因多态性与其代谢相关性无统计学意义。 Objective To study the relationship between occupational hazard susceptibility of formaldehyde and genetic polymorphisms of ALDH2 and CYP2E1. Methods Genotypes of ALDH2 and CYP2E1 (Rsa Ⅰ/Pst Ⅰ site) of 107 subjects exposed to formaldehyde were determined with PCR-RFLP through testing peripheral blood lymphocytes, and the concentration of air formaldehyde in workplace and urine formic acid of the subjects were measured with HPLC. The relationship between genotypes and the urine formic acid increment was analyzed with nonparametric rank sum testing. Results The concentration of urine formic acid increment was related with ALDH2 genotypes ( χ^2 = 9. 241, P 〈 0. 05 ), and the means of urinary formic acid of subjects with GG, GA, AA genotype were ( 15.84 ± 6. 86), ( 12.06 ± 7.94) and (7. 31-±5.37) mg/g creatinine, respectively. Mann-Whitney U test showed the formic acid increment between allele G homozygotes and allele A homozygotes was significantly different ( U = 26, P = 0.033). Our data indicated that the formaldehyde metabolism of ALDH2 GG homozygotic genotype was more active than ALDH2 AA homozygotic genotype( the difference of the two mean rank was 13.30). But the polymorphism of Rsa I / Pst I site of CYP2E1 5′-franking region was not correlated with the concentration of urine formic acid (χ^2= 4. 285, P =0. 117), and the urinary formic acid means of subjects with C1/C1, C1/C2, C2/C2 genotype were ( 11.14 ± 7.91 ), ( 12. 13 ± 8.16 ) and ( 16. 51± 3.78 ) mg/g creatinine, respectively. By Stepwise Multiple Regression Analysis, it showed that the urinary formic acid increment might be influenced by FA exposure concentration and ALDH2 genotype, and the model's R^2 was 0. 196. Condusion The metabolism of formaldehyde in human body was related with the genotypes of ALDH2, but not with the CYP2E1 ( Rsa Ⅰ/Pst Ⅰ ) polymorphisms.
出处 《中华预防医学杂志》 CAS CSCD 北大核心 2008年第8期582-587,共6页 Chinese Journal of Preventive Medicine
基金 基金项目:国家自然科学基金(30471429) 山东省科技攻关项目(2004GG2202153)
关键词 甲醛 甲酸类 醛脱氢酶 NADPH高铁血红素蛋白还原酶 多态现象 遗传 Formaldehyde Formic Acids Aldehyde dehydrogenase NADPH- ferrihemoprotein reductase Polymorphism,genetics
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