AIMS: The sterol regulatory element-binding protein (SREBP)-1c gene has been identified as a susceptibility gene in metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and insulin resistance. Previous studies suggest that SNP17 (rs2297508, exon18c and G952G) of SREBP-1c gene and a common SREBP-1c SNP6 (rs11868035) are associated with an increased risk of T2DM. The present study aimed to confirm the previously reported association in a Chinese population and to examine the two SREBP-1c SNPs for their associations with insulin resistance and blood lipid. METHODS: We genotyped two SREBP-1c SNPs in a case-control study (n=327) from Chinese, including 156 patients with T2DM and 171 healthy controls, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and tested for association with type 2 diabetes, insulin resistance and blood lipid, respectively. Genotype and allele distributions and haplotype construction were analysed. RESULTS: The genotype and allele distributions of rs2297508 and rs11868035 polymorphisms were significantly different in type 2 diabetic patients compared to controls (P=0.002 and P=0.013; 0.00 and 0.001, respectively). Haplotype analyses showed significant association with diabetes risk and confirmed the results of the single SNP analyses. The plasma levels of LDL-c of the minor allele-C carriers of the two SNPs were both significantly higher than the noncarriers in the control group (P<0.05). Furthermore, insulin resistance index (HOMA-IRI) of the rare homozygotes C/C of rs11868035 was significantly lower than that of T/T in the T2DM group (P<0.05). CONCLUSIONS: These findings indicate that the SREBP-1c SNPs rs2297508 and rs11868035 are associated with a significantly increased risk of T2DM and dyslipidemia in the Chinese population. Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabetic patients.
AIMS: The sterol regulatory element-binding protein (SREBP)-1c gene has been identified as a susceptibility gene in metabolic diseases such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and insulin resistance. Previous studies suggest that SNP17 (rs2297508, exon18c and G952G) of SREBP-1c gene and a common SREBP-1c SNP6 (rs11868035) are associated with an increased risk of T2DM. The present study aimed to confirm the previously reported association in a Chinese population and to examine the two SREBP-1c SNPs for their associations with insulin resistance and blood lipid. METHODS: We genotyped two SREBP-1c SNPs in a case-control study (n=327) from Chinese, including 156 patients with T2DM and 171 healthy controls, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and tested for association with type 2 diabetes, insulin resistance and blood lipid, respectively. Genotype and allele distributions and haplotype construction were analysed. RESULTS: The genotype and allele distributions of rs2297508 and rs11868035 polymorphisms were significantly different in type 2 diabeticpatients compared to controls (P=0.002 and P=0.013; 0.00 and 0.001, respectively). Haplotype analyses showed significant association with diabetes risk and confirmed the results of the single SNP analyses. The plasma levels of LDL-c of the minor allele-C carriers of the two SNPs were both significantly higher than the noncarriers in the control group (P<0.05). Furthermore, insulin resistance index (HOMA-IRI) of the rare homozygotes C/C of rs11868035 was significantly lower than that of T/T in the T2DM group (P<0.05). CONCLUSIONS: These findings indicate that the SREBP-1c SNPs rs2297508 and rs11868035 are associated with a significantly increased risk of T2DM and dyslipidemia in the Chinese population. Moreover, the SNP (rs11868035) is closely related to insulin resistance (IR) in diabeticpatients.
Authors: Jane Z Kuo; Wayne Huey-Herng Sheu; Themistocles L Assimes; Yi-Jen Hung; Devin Absher; Yen-Feng Chiu; Jordan Mak; Jun-Sing Wang; Soonil Kwon; Chih-Cheng Hsu; Mark O Goodarzi; I-Te Lee; Joshua W Knowles; Brittany E Miller; Wen-Jane Lee; Jyh-Ming J Juang; Tzung-Dau Wang; Xiuqing Guo; Kent D Taylor; Lee-Ming Chuang; Chao A Hsiung; Thomas Quertermous; Jerome I Rotter; Yii-Der I Chen Journal: Diabetologia Date: 2013-09-08 Impact factor: 10.122