Association of ADIPOQ promoter variants (rs17300539 and rs266729) with glycemic status and serum adiponectin in Egyptian prediabetic and T2DM patients: a case–control study

Promoter polymorphisms rs17300539 (− 11391 G > A) and rs266729 (− 11377 C > G) in the ADIPOQ gene have shown inconsistent associations with circulating adiponectin levels and type 2 diabetes (T2DM) risk across populations, but their role in prediabetes, T2DM, and in Egyptians remains unclear. Therefore, this work investigates how these polymorphisms relate to glycemic status and serum adiponectin levels in Egyptian individuals at the prediabetic stage and with T2DM. A case–control study enrolled 90 Egyptian adults (30 controls, 30 prediabetes, 30 T2DM). Rs17300539 and rs266729 underwent genotyping by using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Serum adiponectin and insulin levels were analysed by enzyme-linked immunosorbent assay (ELISA). Associations between genotypes and glycemic status were analysed by using logistic regression with Firth’s penalized likelihood for sparse data. Differences in adiponectin levels across genotypes were assessed using analysis of covariance (ANCOVA), adjusted for age, sex, and body mass index (BMI). The rs17300539 A allele and GA genotype were more frequent in prediabetes and T2DM. Under a dominant model, rs17300539 was strongly associated with prediabetes (adjusted OR = 20.92, p = 0.038), whereas its effect in T2DM was modest and not statistically significant after adjustment (adjusted OR = 1.36, p = 0.909). A-allele carriers of rs17300539 had lower adiponectin, but differences were not significant (prediabetes: median 2.90 vs. 2.80 ng/ml, adjusted p = 0.982; T2DM: median 1.90 vs. 3.60 ng/ml, adjusted p = 0.456). For rs266729, the variant genotype (CG + GG) was not significantly associated with disease risk (prediabetes: adjusted OR=1.12, p=0.906; T2DM: adjusted OR=0.04, p= 0.269). However, among T2DM patients, variant carriers had significantly lower adjusted adiponectin levels than wild-type individuals (median 2.50 vs. 3.95 ng/ml, adjusted p= 0.010). The ADIPOQ rs17300539 confers susceptibility to early glucose dysregulation, particularly prediabetes, independently of adiponectin, suggesting effects via alternative metabolic pathways. In contrast, rs266729 appears to primarily influence serum adiponectin concentration in individuals with established T2DM, without a strong independent effect on disease risk. These findings underscore the importance of disease stage, adiposity, and ethnic background when interpreting ADIPOQ genetic associations.