Ensiyeh Seyedrezazadeh - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Elnaz Faramarzi - Liver and Gastrointestinal Diseases Research Center, Clinical Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
Nasim Bakhtiyari - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Atefeh Ansarin - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Neda Gilani - Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran
Amir Amiri-Sadeghan - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Maryam Seyyedi - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Khalil Ansarin - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Younes Aftabi - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Objective(s): We investigated whether NOS۳-c.۸۹۴G>T transversion (rs۱۷۹۹۹۸۳), which causes the substitution of glutamate with aspartate (E۲۹۸D) in the oxygenase domain of endothelial nitric oxide synthase (eNOS), is associated with susceptibility to metabolic syndrome (MetS) risk in Iranian-Azerbaijanis. Materials and Methods: The frequencies of the alleles and genotypes were compared in the ۳۰۰ cases and ۳۰۰ controls using PCR-RFLP assay. Also, higher-order MetS interaction with the genotypes, gender, age, and body mass index (BMI) was evaluated by classification and regression tree (CART) analysis. In silico analysis was done to introduce a hypothesis describing the molecular effects of NOS۳-c.۸۹۴G>T. Results: The T allele (OR:۱.۴۶; CI:۱.۰۵۴-۲.۰۴; P=۰.۰۲), GT genotype (OR:۱.۴۴; CI:۱.۰۲-۲.۰۳; P=۰.۰۳), and dominant model (TT+GT vs GG, OR:۱.۴۸; CI:۱.۰۶-۲.۰۶; P=۰.۰۱) were found to be associated with increased risk of MetS. In the male subpopulation TT genotype (OR:۷.۱۹; CI:۱.۵۳-۳۳.۷۰; P=۰.۰۱) was discovered to be associated with increased odds of MetS. CART analysis showed that NOS۳-c.۸۹۴G>T genotypes and BMI significantly contribute to modulating MetS risk. Furthermore, in silico investigation revealed that c.۸۹۴G>T may alter eNOS function through affecting interactions of its oxygenase domain with proteins such as B۲R, b-actin, CALM۱, CAV۱, GIT۱, HSP۹۰AA۱, NOSIP, and NOSTRIN. Conclusion: We showed that NOS۳-c.۸۹۴G>T was associated with an increased risk of MetS in Iranian-Azerbaijanis, and BMI modulates the effects of NOS۳-c.۸۹۴G>T genotypes on MetS risk. Also, in silico analysis found that NOS۳-c.۸۹۴G>T may affect the interaction of the eNOS oxygenase domain with its several functional partners.

Azar, cohort Bioinformatics Metabolic syndrome Nitric oxide pathway rs۱۷۹۹۹۸۳