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Objective To observe the G-395A polymorphisms of Klotho gene in type 2 diabetes mellitus ( T2DM) pa-tients, and to investigate its influence on combined lower limb atherosclerosis. Methods The G-395A polymorphisms of Klotho gene from 205 cases of normal controls (85 cases of Han nationality, 120 cases of Yi nationality, control group), 140 cases of T2DM patients (79 cases of Han nationality, 61 cases of Yi nationality, T2DM group) and 224 cases of patients with lower limb atherosclerosis combined with T2DM (157 cases of Han nationality, 67 cases of Yi nationality, atherosclerosis group) were detected by real-time fluorescence quantification PCR ( FQ-PCR) .The genotype frequency and allele frequency were compared between each group, and the risk factors of T2DM combined with lower limb atherosclerosis were analyzed. Results The genotype frequency of Klotho gene G-395A site G/A+A/A in the atherosclerosis group of Han nationality was higher than that of Yi nationality (P<0.05).There was no significant difference in genotype and allele frequency among the rest groups (all P>0.05).The influence factors of T2DM patients with lower extremity atherosclerosis in Han nationality were systolic blood pressure, TG, LHL, fasting blood-glucose ( FPG) and genotype of Klotho gene G-395A site G/A+A/A (all P<0.05).The influence factors of T2DM patients with lower extremity atherosclerosis in Yi nationality were TG, LHL, FPG and serum creatinine (all P<0.05).Conclusions There is gene polymorphism at G-395A of Klotho gene in T2DM patients with lower limb atherosclerosis. The Klotho gene G-395A site G/A+A/A genotype may be a genetic risk factor for the occurrence of lower limb atherosclerosis of T2DM patients in Han nationality. [ABSTRACT FROM AUTHOR]