Objective:To examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus (T2DM).Methods:A matched case-control study was performed to investigate the association between common variants in four genes (CDKAL1,GLIS3,GRK5,and TCF7L2) and symptoms of T2DM.Symptoms were examined with questionnaire for 710 subjects.Genomic DNA was extracted from peripheral blood mononuclear cell by salting-out procedure.Genotyping was carried out by direct sequencing of the unpurified polymerase chain reaction products.Result:Most of the T2DM patients pressented characteristic symptoms,such as feeling weak in limbs (P=0.0057),hand tremor (P=0.0208),bradymasesis (P=0.0234),and polyuria (P=0.0051).Some of the T2DM patients shared characteristic symptoms,such as desire for cold drinks (P=0.0304),polyphagia (P=0.0051),and furred tongue (P=0.028).The impaired glucose regulation (IGR) cases took only one characteristic symptom of frequent micturition (P=0.0422).GLIS3 rs7034200 and GRK5 rs10886471 were significantly associated with increased T2DM risk (GLIS3 rs7034200 under dominant model:P=0.0307;GRK5 rs10886471 under recessive model:P=0.0092).However,only the rs10886471 polymorphism in GRK5 showed a significant effect on both differentiated symptoms and T2DM risk.The C-allele was involved in both dampness-heat encumbering Pi (Spleen)syndrome (P=0.047) and qi-yin deficiency syndrome (P=0.002) via increased GRK5 expression.Conclusions:Both T2DM and IGR exhibited its corresponding characteristic symptoms.The variants of GRK5 were involved with both qi-yin deficiency syndrome and dampness-heat encumbering Pi syndrome.