Arif Ehtesham, Vibhuti Arpana, Alam Pervez, Deepak Desh, Singh Bhawani, Athar Mohammad, Pasha M A Qadar
Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India.
Clin Chim Acta. 2007 Jul;382(1-2):37-42. doi: 10.1016/j.cca.2007.03.013. Epub 2007 Mar 24.
Detoxification genes are potential candidates in the susceptibility of patients with chronic obstructive pulmonary disease. Polymorphisms in these genes alter the metabolism of xenobiotics such as present in cigarette smoke.
We conducted a case-control study to investigate total 9 polymorphisms of CYP2E1, CYP2D6 and NAT2 genes by PCR-RFLP.
The -1053C/T and -1293G/C promoter polymorphisms of CYP2E1 were found to be in complete linkage disequilibrium (LD) (D'=1.00, r(2)=1.0, p<0.0001), whereas -1293G/C and 7632T/A polymorphisms of the same gene were also in significant LD (D'=0.5183, r(2)=1.0, p=0.01) in patients. The patients over-represented the -1293GC+CC genotypes of -1293G/C polymorphism of CYP2E1 (p=0.03) and NAT2*4/7, NAT2()5/6, NAT2*5/7, NAT2*6/6 and NAT2*6/7 genotypes of NAT2 (p=0.01, p=0.039, p=0.01, p=0.032, p=0.006, respectively), resulting in to higher frequency of -1293C (OR=7.02, 95% CI=1.63-30.15, p=0.002), NAT2*6 (OR=1.90, 95% CI=1.27-2.83, p=0.001) and NAT2*7 (OR=2.91, 95% CI=1.65-5.12, p=0.0001) alleles. The 7632T/A and 9893C/G polymorphisms of CYP2E1 and 1934G/A polymorphism of CYP2D6 did not associate with the disease (p>0.05). The haplotypes -1293G:9893C and -1293G:7632T:9893C were under-represented (p<0.001), whereas haplotypes -1293C:7632T, -1293C:9893C, -1293C:9893G and -1293C:7632T:9893C of the 4 CYP2E1 polymorphisms were over-represented in patients (p<0.05).
The CYP2E1 and NAT2 variants associated with COPD.
解毒基因是慢性阻塞性肺疾病患者易感性的潜在候选基因。这些基因的多态性会改变香烟烟雾中存在的外源性物质的代谢。
我们进行了一项病例对照研究，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）来研究CYP2E1、CYP2D6和NAT2基因的总共9种多态性。
发现CYP2E1的-1053C/T和-1293G/C启动子多态性处于完全连锁不平衡（LD）状态（D'=1.00，r(2)=1.0，p<0.0001），而同一基因的-1293G/C和7632T/A多态性在患者中也处于显著的LD状态（D'=0.5183，r(2)=1.0，p=0.01）。患者中CYP2E1的-1293G/C多态性的-1293GC+CC基因型（p=0.03）以及NAT2的NAT2*4/7、NAT2()5/6、NAT2*5/7、NAT2*6/6和NAT2*6/7基因型（分别为p=0.01、p=0.039、p=0.01、p=0.032、p=0.006）过度表达，导致-1293C（优势比[OR]=7.02，95%置信区间[CI]=1.63 - 30.15，p=0.002）、NAT2*6（OR=1.90，95%CI=1.27 - 2.83，p=0.001）和NAT2*7（OR=2.91，95%CI=1.65 - 5.12，p=0.0001）等位基因的频率更高。CYP2E1的7632T/A和9893C/G多态性以及CYP2D6的1934G/A多态性与该疾病无关（p>0.05）。单倍型-1293G:9893C和-1293G:7632T:9893C的表达不足（p<0.001），而4种CYP2E1多态性的单倍型-1293C:7632T、-1293C:9893C、-1293C:9893G和-1293C:7632T:9893C在患者中过度表达（p<0.05）。
CYP2E1和NAT2变体与慢性阻塞性肺疾病相关。
