The T-786C, G894T, and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in prostate cancer cases

The T-786C, G894T, and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in prostate cancer cases
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DOI:
10.1134/s1022795416020022
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发表时间:
2016-02-01
影响因子:
0.6
通讯作者:
Oden, A.
Oden, A.
中科院分区:
生物学4区
文献类型:
--
作者:
Diler, S. B.;Oden, A.

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在以往的一些研究中发现,一氧化氮(NO)和一氧化氮合酶(NOS)系统在致癌过程中起着重要作用。一氧化氮(NO)是由一氧化氮合酶(NOS)同工酶之一的内皮型一氧化氮合酶(eNOS)调控的。本研究试图探讨eNOS基因T-786C、G894T和内含子4 VNTR (4a/b)多态性是否可作为前列腺癌(PCa)的危险因素。本研究共纳入200名受试者。84例PCa患者(平均年龄70.0 +/- 6.4岁)和116名健康对照者(平均年龄69.9 +/- 7.5岁)参与了这项病例对照研究。基因组DNA提取使用QIAamp DNA血液迷你试剂盒(QIAGEN GmbH, Maryland, USA),根据制造商的指导方针。采用聚合酶链反应(PCR)扩增T-786C、G894T和内含子4 VNTR (4a/b)多态性,采用限制性片段长度多态性(RFLP)检测。对于T-786C多态性,CC基因型[比值比(OR): 0.34, 95%可信区间(CI): 0.15 ~ 0.78, P = 0.009]和等位基因频率(OR: 0.631, CI: 0.421 ~ 0.946, P = 0.026)在对照中具有显著性。在PCa eNOS G894T多态性患者中,GT (OR: 0.069, CI: 0.027-0.174, P = 0.0001)和TT (OR: 0.040, CI: 0.013-0.123, P = 0.0001)基因型分布和T等位基因频率(OR: 0.237, CI: 0.155-0.362, P = 0.0001)均认为具有统计学意义。另一多态性eNOS内含子4 VNTR (4a/b)的基因型分布在统计学上不显著,而“a”等位基因频率显著(OR: 2.223, CI: 1.311 ~ 3.769, P = 0.003)。在本研究中,我们发现eNOS T-786C和G894T多态性的基因型和等位基因频率在PCa患者中具有统计学意义。eNOS T-786C和G894T多态性可能与土耳其人群的PCa易感性有关。相反,在这些患者中,内含子4 VNTR (4a/b)多态性可能与PCa易感性无关。
In previously conducted some studies it has been revealed that nitric oxide (NO) and nitric oxide synthase (NOS) system play a significant role in carcinogenesis. Nitric oxide (NO) is regulated by endothelial nitric oxide synthase (eNOS) enzyme which is one of the isoenzymes of NO synthase (NOS). In this study we have tried to come to a conclusion about whether eNOS gene T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms might be considered as a risk factor causing prostate cancer (PCa) or not. A total of 200 subjects were included in this research. 84 patients with PCa (mean age 70.0 +/- 6.4) and 116 healthy controls (mean age 69.9 +/- 7.5) were recruited in this case-control study. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (QIAGEN GmbH, Maryland, USA), according to the manufacturer's guidelines. The T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms were amplified using polymerase chain reation (PCR), detected by restriction fragment length polymorphism (RFLP). For T-786C polymorphism CC genotype [odds ratio (OR): 0.34, 95% confidence interval (CI): 0.15-0.78, P = 0.009)] and allele frequency (OR: 0.631, CI: 0.421-0.946, P = 0.026) is significant for control. In patients with PCa eNOS G894T polymorphism, both GT (OR: 0.069, CI: 0.027-0.174; P = 0.0001) and TT (OR: 0.040, CI: 0.013-0.123; P = 0.0001) genotype distribution, and also T allele frequency (OR: 0.237, CI: 0.155-0.362, P = 0.0001) were considered significant statistically. While genotype distribution for the other polymorphism eNOS, intron 4 VNTR (4a/b), is insignificant statistically, "a" allele frequency was found out to be significant (OR: 2.223, CI: 1.311-3.769, P = 0.003). In this study we indicated that genotype and allele frequencies of eNOS T-786C and G894T polymorphisms are statistically significant in patients with PCa. eNOS T-786C and G894T polymorphisms may be associated with PCa susceptibility in the Turkish population. In contrast, intron 4 VNTR (4a/b) polymorphism may not be related to PCa susceptibility in these patients.