Cheng Xue-mei, Zhao Jing, Feng Bin, Wen Pei-e, Shao Hua
Shandong Academy of Occupational Health and Occupational Diseases, Jinan, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2008 Aug;42(8):582-7.
To study the relationship between occupational hazard susceptibility of formaldehyde and genetic polymorphisms of ALDH2 and CYP2E1.
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.
The concentration of urine formic acid increment was related with ALDH2 genotypes (chi2 = 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 (chi2 = 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 R2 was 0.196.
The metabolism of formaldehyde in human body was related with the genotypes of ALDH2, but not with the CYP2E1 (Rsa I/Pst I) polymorphisms.
研究甲醛职业危害易感性与乙醛脱氢酶2(ALDH2)和细胞色素P450 2E1(CYP2E1)基因多态性的关系。
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测107名甲醛接触者外周血淋巴细胞中ALDH2和CYP2E1(Rsa I/Pst I位点)的基因型,用高效液相色谱法(HPLC)测定工作场所空气中甲醛浓度及受试者尿中甲酸浓度。采用非参数秩和检验分析基因型与尿甲酸增加值的关系。
尿甲酸增加值与ALDH2基因型有关(χ2 = 9.241,P < 0.05),GG、GA、AA基因型受试者尿甲酸均值分别为(15.84±6.86)、(12.06±7.94)和(7.31±5.37)mg/g肌酐。Mann-Whitney U检验显示,等位基因G纯合子与等位基因A纯合子之间的甲酸增加值差异有统计学意义(U = 26,P = 0.033)。结果表明,ALDH2 GG纯合基因型的甲醛代谢活性高于ALDH2 AA纯合基因型(两个平均秩次之差为13.30)。但CYP2E1 5′-侧翼区Rsa I / Pst I位点多态性与尿甲酸浓度无关(χ2 = 4.285,P = 0.117),C1/C1、C1/C2、C2/C2基因型受试者尿甲酸均值分别为(11.14±7.91)、(12.13±8.16)和(16.51±3.78)mg/g肌酐。逐步多元回归分析显示,尿甲酸增加值可能受甲醛接触浓度和ALDH2基因型的影响,模型的R2为0.196。
人体甲醛代谢与ALDH2基因型有关,而与CYP2E1(Rsa I/Pst I)多态性无关。