Objective To investigate the relationship between single nucleotide polymorphism(SNP) C1330T of syndecan-3(SDC3) gene and hypercholesterolemia,lipid profile in a Chinese rural population.Methods Hypercholesterolemia(HTC) was defined as serum total cholesterol equal to or more than 200 mg/dL.Genotyping for C1330T was completed by using PCR,restrictive enzyme digestion,and sequencing in 336 males(HTC 161,normal total cholesterol(NTC) 175),1491 females(HTC 935, NTC 556).Serum total cholesterol(TC),HDL-cholesterol(HDL-C),LDL-cholesterol(LDL-C),triglyceride(TG),glucose(Glu) level were measured.Results The significant difference of distribution of C1330T was observed between HTC and NTC in males.1330C was associated with HTC in men(odds ratios(OR)=1.42,95% confidence intervals(CI)=1.040-1.926,P< 0.03),but not in women(OR=1.06,95%CI=0.92-1.24,P=0.41). After adjusted by age,body mass index(BMI) and other conventional risk factors,the association remained in men.For 1330C,there was a borderline statistically significant allele*gender interaction(P=0.0742).The association between C1330T and serum HDL-C,LDL-C level were observed in men.Conclusion The distribution of C1330T of SDC3 gene was associated with hypercholesterolemia,lipid profile in men.