Ben Nasr Hela, Bchir Sarra, Ben Anes Amel, Amri Asma, Sakhana Yosra, Benzarti Mohamed, Garrouch Abdelhamid, Tabka Zouhair, Chahed Karim
Unité de Recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire "Biologie, Medecine et Santé, Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia; Institut des Sciences Infirmières de Sousse, Tunisia.
Unité de Recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie: de l'Intégré au Moléculaire "Biologie, Medecine et Santé, Faculté de Medecine Ibn el Jazzar, Sousse, Tunisia.
Cytokine. 2017 May;93:66-73. doi: 10.1016/j.cyto.2017.05.010. Epub 2017 May 16.
The goal of this study was to examine the role of G894T (rs1799983), -786T/C (rs3918161) and a 27 bp variable number of tandem repeats (VNTR) 4B/4A of NOS3 gene on the risk and severity of COPD.
The study included 194 controls and 138 COPD patients. NOS3 G894T, -786T/C and 4B/4A variants were determined by PCR analysis based on the banding pattern on gel electrophoresis. Pulmonary function was evaluated using body plethysmography. The levels of nitric oxide, peroxynitrite and lipid peroxides (T-BARS) were determined using spectrophotometric methods. Levels of serum IL-6, TNF-α and TGFβ were determined by ELISA.
In case-control studies, both G894T and -786T/C variants were associated with COPD risk. A significantly increased risk of COPD was found with the NOS3894T and -786C alleles (OR:1.93, P=0.001; OR:2.05, P=0.001, respectively). No significant impact of the G894T and 4B/4A SNPs was found on COPD severity, while a significant correlation was retrieved between the NOS3 -786T/C variation and advanced stages (OR: 1.89, P=0.009). In addition, COPD patients with the -786CC genotype exhibited lower FEV1% values in comparison to -786TT carriers (48±3.28 vs. 58.06±2.3, P=0.01, respectively). Patients having the -786CC genotype presented lower plasma levels of nitric oxide and higher T-BARS in comparison to -786TT individuals (173.22±13.4 vs. 228.93±16.8, P=0.01; 1.8±0.15 vs. 1.22±0.15, P=0.01, respectively).
This study provides the first evidence for the association of G894T, -786T/C variants with COPD risk among Tunisians. The -786T/C variation correlates with enhanced airflow limitation. This finding could be related to altered levels of nitric oxide and enhanced lipid peroxides among patients carrying the -786CC genotype.
本研究旨在探讨一氧化氮合酶3（NOS3）基因的G894T（rs1799983）、-786T/C（rs3918161）以及一个27bp可变数目串联重复序列（VNTR）4B/4A在慢性阻塞性肺疾病（COPD）风险及严重程度中的作用。
该研究纳入了194名对照者和138名COPD患者。基于凝胶电泳条带模式，通过聚合酶链反应（PCR）分析确定NOS3基因的G894T、-786T/C及4B/4A变异。使用体容积描记法评估肺功能。采用分光光度法测定一氧化氮、过氧亚硝酸盐和脂质过氧化物（硫代巴比妥酸反应物，T-BARS）水平。通过酶联免疫吸附测定法（ELISA）测定血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGFβ）水平。
在病例对照研究中，G894T和-786T/C变异均与COPD风险相关。发现携带NOS3 894T和-786C等位基因会使COPD风险显著增加（比值比：1.93，P = 0.001；比值比：2.05，P = 0.001）。未发现G894T和4B/4A单核苷酸多态性（SNP）对COPD严重程度有显著影响，而NOS3 -786T/C变异与疾病晚期显著相关（比值比：1.89，P = 0.009）。此外，与-786TT携带者相比，-786CC基因型的COPD患者第一秒用力呼气容积占预计值百分比（FEV1%）更低（分别为48±3.28 vs. 58.06±2.3，P = 0.01）。与-786TT个体相比，-786CC基因型患者的血浆一氧化氮水平更低，T-BARS水平更高（分别为173.22±13.4 vs. 228.93±16.8，P = 0.01；1.8±0.15 vs. 1.22±0.15，P = 0.01）。
本研究首次提供了在突尼斯人群中G894T、-786T/C变异与COPD风险相关的证据。-786T/C变异与气流受限加重相关。这一发现可能与携带-786CC基因型患者一氧化氮水平改变及脂质过氧化物增加有关。
