The -786 T/C polymorphism of NOS3 gene is a susceptibility marker of COPD among Tunisians that correlates with nitric oxide levels and airflow obstruction
| Autor: | Zouhair Tabka, Asma Amri, Mohamed Benzarti, Yosra Sakhana, Hela Ben Nasr, Amel ben Anes, Abdelhamid Garrouch, Karim Chahed, Sarra Bchir |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Genetic Markers
Male 0301 basic medicine medicine.medical_specialty Pathology Tunisia Nitric Oxide Synthase Type III Immunology Single-nucleotide polymorphism Nitric Oxide Polymorphism Single Nucleotide Biochemistry Gastroenterology Pulmonary function testing Nitric oxide Pulmonary Disease Chronic Obstructive 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Genotype Humans Immunology and Allergy Medicine Plethysmograph Genetic Predisposition to Disease Allele Molecular Biology Aged COPD business.industry Hematology Middle Aged medicine.disease Variable number tandem repeat 030104 developmental biology 030228 respiratory system chemistry Female business |
| Zdroj: | Cytokine. 93:66-73 |
| ISSN: | 1043-4666 |
| DOI: | 10.1016/j.cyto.2017.05.010 |
| Popis: | Objective 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. Methods 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. Results 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 NOS3 894T 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). Conclusion 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. |
| Databáze: | OpenAIRE |
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