Association of NOS3-c.894G>T transversion with susceptibility to metabolic syndrome in Azar-cohort population: A case-control study and in silico analysis of the SNP molecular effects | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 17، دوره 24، شماره 3، خرداد 2021، صفحه 408-419 اصل مقاله (1.21 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2021.50528.11511 | ||
| نویسندگان | ||
| Ensiyeh Seyedrezazadeh1؛ Elnaz Faramarzi2؛ Nasim Bakhtiyari1؛ Atefeh Ansarin1؛ Neda Gilani3؛ Amir Amiri-Sadeghan1؛ Maryam Seyyedi1؛ Khalil Ansarin1؛ Younes Aftabi* 1 | ||
| 1Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 2Liver and Gastrointestinal Diseases Research Center, Clinical Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 3Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| چکیده | ||
| Objective(s): We investigated whether NOS3-c.894G>T transversion (rs1799983), which causes the substitution of glutamate with aspartate (E298D) 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 300 cases and 300 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 NOS3-c.894G>T. Results: The T allele (OR:1.46; CI:1.054-2.04; P=0.02), GT genotype (OR:1.44; CI:1.02-2.03; P=0.03), and dominant model (TT+GT vs GG, OR:1.48; CI:1.06-2.06; P=0.01) were found to be associated with increased risk of MetS. In the male subpopulation TT genotype (OR:7.19; CI:1.53-33.70; P=0.01) was discovered to be associated with increased odds of MetS. CART analysis showed that NOS3-c.894G>T genotypes and BMI significantly contribute to modulating MetS risk. Furthermore, in silico investigation revealed that c.894G>T may alter eNOS function through affecting interactions of its oxygenase domain with proteins such as B2R, b-actin, CALM1, CAV1, GIT1, HSP90AA1, NOSIP, and NOSTRIN. Conclusion: We showed that NOS3-c.894G>T was associated with an increased risk of MetS in Iranian-Azerbaijanis, and BMI modulates the effects of NOS3-c.894G>T genotypes on MetS risk. Also, in silico analysis found that NOS3-c.894G>T may affect the interaction of the eNOS oxygenase domain with its several functional partners. | ||
| کلیدواژهها | ||
| Azar؛ cohort Bioinformatics Metabolic syndrome Nitric oxide pathway rs1799983 | ||
| مراجع | ||
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