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ObjectiveTo investigate the effect of the interaction between single nucleotide polymorphisms （SNPs） of EXT2 gene and KCNJ11 gene and blood glucose on the susceptibility to metabolic syndrome （MS） with yin deficiency pattern.Methods216 patients with MS （108 cases with yin deficiency pattern and 108 cases with non-yin deficiency pattern） and 235 healthy people were recruited. Multiple SNP typing techniques were used to detect SNPs in the subjects. SHEsis software was used to analyze the genes of the three groups of participants. A Generalized Multifactor Dimensionality Reduction （GMDR） combined with logistic regression model was used to detect the effect of the interaction between SNPs and blood glucose on MS with yin deficiency pattern.ResultsIndividuals with KCNJ11 gene rs5215-C allelic polymorphism （CT+CC） had a 0.947 times higher risk of contracting MS with yin deficiency pattern compared with those with TT （P > 0.05）. Individuals with EXT2 gene rs11037909-C allelic polymorphism （CT+CC） had a 1.839 times higher risk of contracting MS compared with those with TT （P＜0.05）. The model composed of EXT2 gene rs11037909-C and blood glucose was the best model related to the risk of MS with yin deficiency pattern （P = 0.0010）. Individuals with CT/CC genotype but without hyperglycemia had a 4.216 times higher risk of contracting MS with yin deficiency pattern compared with those with TT genotype but without hyperglycemia （P < 0.05）. Individuals with hyperglycemia and TT genotype had a 3.737 times higher risk of contracting MS with yin deficiency pattern compared with those with the same genotype but without hyperglycemia. （P < 0.05）.ConclusionCarrying the rs5215-C allele of KCNJ11 gene does not seem to increase the susceptibility to MS with yin deficiency pattern. While the rs11037909-C allele of EXT2 gene is a likely risk factor for MS， and the interaction between rs11037909 of EXT2 gene and blood glucose probably increase the susceptibility to MS with yin deficiency pattern. Both rs11037909-C allele and hyperglycemia are risk factors for MS with yin deficiency pattern； with the interaction of them， the risk of developing MS with yin deficiency pattern is likely to be higher than those without either risk factor.