Background/aim: Genetic predisposition is implicated in the etiology of metabolic syndrome. This study aimed to investigate the association of vaspin rs2236242 and leptin rs7799039 polymorphisms with their serum levels and with the risk of developing metabolic syndrome in Egyptian women. Materials and methods:This case control study included 100 Egyptian women with metabolic syndrome and 100 without metabolic syndrome. The genotypes of vaspin rs2236242 and leptin rs7799039 were detected by a methodology based on PCR-RFLP. Serum vaspin and leptin levels were determined by ELISA. Results:The metabolic syndrome group was associated with higher serum vaspin and leptin levels when compared to the nonmetabolic syndrome group. The AA genotype of leptin rs7799039 was associated with metabolic syndrome and with higher serum leptin levels, while the different genotypes of vaspin rs2236242 were not associated with metabolic syndrome or different serum vaspin levels. Conclusion:The AA genotype of leptin rs7799039 was associated with metabolic syndrome and higher serum leptin levels. Serum leptin and vaspin can be used as diagnostic markers of metabolic syndrome.