Journal of Advances in Medical and Biomedical Research

en Associations of Sex Hormone-Binding Globulin Gene Polymorphisms and Circulating Levels with Metabolic Dysfunction in an Iraqi Population: A Case-Control Study Clinical Medicine Clinical Medicine مقاله پژوهشی Original Research Article Background & Objective:  Sex hormone-binding globulin has recently emerged as a promising biomarker and is increasingly recognized as a potential predictor of type 2 diabetes mellitus (T2DM) and metabolic dysfunction. Genetic polymorphisms in the SHBG gene may influence circulating SHBG concentrations, thereby contributing to susceptibility to metabolic disorders. This study aimed to investigate the association between SHBG gene polymorphisms, circulating SHBG levels, and metabolic dysfunction in an Iraqi population.  Materials & Methods:  This case-control study included 600 participants. Serum SHBG concentrations were quantified using a commercially available enzyme-linked immunosorbent assay (ELISA), while other biological parameters were measured using standardized laboratory methods. Genotyping of the SHBG polymorphisms rs1799941 and rs6257 was performed using TaqMan real-time polymerase chain reaction assays. Statistical analyses included the chi-square test, multinomial logistic regression, two-way analysis of covariance (ANCOVA), and ROC curve analysis to evaluate genotype distributions, associations, and the diagnostic performance of circulating SHBG levels. Results:  Serum SHBG concentrations decreased progressively across the metabolic continuum, from healthy controls to individuals with insulin resistance (IR) and patients with T2DM (P < 0.001). Genotype distribution analysis revealed that the rs1799941 AA and rs6257 CC genotypes were significantly associated with an increased susceptibility to T2DM (P < 0.001). Furthermore, both polymorphisms independently influenced circulating SHBG concentrations (P = 4.7 × 10⁻¹² and P = 0.03, respectively). Circulating SHBG demonstrated excellent discriminatory performance for distinguishing patients with T2DM from healthy controls, with an area under the curve (AUC) of 0.928 (95% CI: 0.903–0.953). Conclusion:  A significant association was observed between decreased circulating SHBG concentrations and metabolic changes or T2DM. Both concentrations of SHBG in serum and risk of T2DM are independently correlated with the SHBG polymorphisms rs1799941 and rs6257.   Sex hormone-binding globulin, rs1799941, rs6257, insulin resistance, type 2 diabetes mellitus. 281 292 http://journal.zums.ac.ir/browse.php?a_code=A-10-7417-2&slc_lang=en&sid=1 Hazim Ali Hussein hazim.ali@jmu.edu.iq 5200319475328460090761 0009-0000-1267-5097 No Department of Clinical Laboratory Sciences, College of Pharmacy, Jabir Ibn Hayyan University for Medical and Pharmaceutical Sciences, Iraq Mohammed N. Salman mohammed.noori@jmu.edu.iq 5200319475328460090762 5200319475328460090762 Yes Department of Clinical Laboratory Sciences, College of Pharmacy, Jabir Ibn Hayyan University for Medical and Pharmaceutical Sciences, Iraq Abdulhussein Alwan Algenabi aalhussein.aljanabi@uokufa.edu.iq 5200319475328460090763 5200319475328460090763 No Department of Biochemistry, College of Medicine, Kufa University, Iraq