Diabetes mellitus, particularly Type 2 diabetes mellitus (T2DM), is a prevalent metabolic disorder with significant health implications. This study aimed to investigate the association between spexin (SPX) gene polymorphisms and serum Spexin levels in Iraqi women with T2DM. A case–control study was conducted involving 100 diabetic patients and 100 healthy controls, with data collected on biochemical parameters such as fasting blood sugar (FBS), body mass index (BMI), and lipid profiles. Genomic DNA was extracted, and Sanger sequencing was performed to identify SNPs in the SPX gene. Significant differences in BMI, FBS, LDL, and Spexin levels were observed between the T2DM and control groups (p < 0.05). Among the analyzed SNPs, rs761986956 showed a significant association with T2DM, where the G allele increased susceptibility (p 0.04, OR 2.62, 95% CI 1–6.8). Additionally, rs1214680179 exhibited a borderline association with T2DM (p 0.05) and was linked to lower serum Spexin concentrations, suggesting a possible role in metabolic regulation. In contrast, rs780278792, rs1413328860, and rs772766676 showed no significant association with T2DM susceptibility (p > 0.05). These findings suggest that rs761986956 and potentially rs1214680179 may contribute to T2DM pathogenesis, emphasizing the role of genetic factors in disease development. Furthermore, they highlight the importance of studying SPX gene polymorphisms as potential biomarkers for diabetes management in the Iraqi population. Given the preliminary nature of some associations, further research with larger, more diverse cohorts is needed to validate these findings and clarify their biological implications.
