Allele-specific transcriptional activity of the variable number of tandem repeats of the inducible nitric oxide synthase gene is associated with idiopathic achalasia
Allele-specific transcriptional activity of the variable number of tandem repeats of the inducible nitric oxide synthase gene is associated with idiopathic achalasia
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DOI：
10.1177/2050640616648870
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发表时间：
2017-03-01
影响因子：
6
通讯作者：
Cuomo, Rosario
中科院分区：
文献类型：
--
作者：
Sarnelli, Giovanni;Grosso, Michela;Cuomo, Rosario
背景：参与免疫反应调节的基因多态性是贲门失弛缓症的危险因素，但它们对疾病发病机制的贡献尚不清楚。一氧化氮参与免疫功能和抑制性神经传递。目的：本文的目的是评估贲门失弛缓症中 CCTTT 诱导型一氧化氮合酶 (NOS2) 基因启动子多态性的关联和功能相关性。方法：从 181 名贲门失弛缓症患者和 220 名对照者中分离基因组 DNA。通过 PCR 和毛细管电泳对 (CCTTT)n 重复序列进行基因分型，并通过考虑不同等位基因的频率来分析数据。用含有不同(CCTTT)n的iNOS荧光素酶启动子-报告基因质粒转染HT29细胞。结果：等位基因分布范围为7～18个，峰值频率为12次重复。等位基因频率分析显示，携带 10 个和 13 个 CCTTT 重复的个体患贲门失弛缓症的频率分别较低和较高（OR 0.5，95% CI 0.3-0.5 和 OR 1.6，95% CI 1-2.4，所有 p
Background: Polymorphisms of genes involved in the regulation of the immune response are risk factors for achalasia, but their contribution to disease pathogenesis is unknown. Nitric oxide is involved both in immune function and inhibitory neurotransmission.Objective: The objective of this article is to assess the association and the functional relevance of the CCTTT-inducible nitric oxide synthase (NOS2) gene promoter polymorphism in achalasia.Methods: Genomic DNA was isolated from 181 achalasia patients and 220 controls. Genotyping of the (CCTTT)n repeats was performed by PCR and capillary electrophoresis, and data analyzed by considering the frequency of the different alleles. HT29 cells were transfected with iNOS luciferase promoter-reporter plasmids containing different (CCTTT)n.Results: The alleles' distribution ranged from 7 to 18, with a peak frequency at 12 repeats. Analysis of the allele frequencies revealed that individuals carrying 10 and 13 CCTTT repeats were respectively less and more frequent in achalasia (OR 0.5, 95% CI 0.3-0.5 and OR 1.6, 95% CI 1-2.4, all p