The -786 T/C polymorphism ofNOS3gene is a susceptibility marker of COPD among Tunisians that correlates with nitric oxide levels and airflow obstruction

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Abstract

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.

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