Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes.
Polymorphisms in the gene encoding sterol regulatory element-binding factor-1c are associated with type 2 diabetes.
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DOI：
10.1007/s00125-006-0430-1
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发表时间：
2006-11
期刊：
影响因子：
8.2
通讯作者：
Barroso, I.
中科院分区：
文献类型：
--
作者：
Harding, A. -H.;Loos, R. J. F.;Luan, J.;O'Rahilly, S.;Wareham, N. J.;Barroso, I.
关键词：
固醇调节元件结合因子（SREBF）-1c是一种参与调节脂质和葡萄糖代谢的转录因子。我们之前发现的证据表明，位于外显子18 c和19 c之间的常见SREBF 1c单核苷酸多态性（SNP）与2型糖尿病风险增加有关。本研究旨在复制我们以前报道的关联在一个更大的病例对照研究，并检查额外的5个SREBF 1c SNPs与糖尿病风险和血糖浓度的关联。我们在两项病例对照研究（n= 1，938）和一项大型队列研究（n= 1，721）中对6个SREBF 1c SNP进行了基因分型，并分别检测了其与2型糖尿病和血糖浓度（空腹和葡萄糖负荷后120分钟）的相关性。在病例对照研究中，先前报道的SNP（rs 11868035）的次要等位基因的携带者具有显著增加的糖尿病风险（比值比[OR]=1.20 [95%CI 1.04-1.38]，p=0.015）。此外，位于5′区的其他三个SNP（rs 2236513，rs6502618和rs 1889018）与糖尿病风险显著相关（OR ≥1.21，p≤0.006）。此外，在队列研究中，5′区的两个SNP（rs 2236513和rs 1889018）与血浆葡萄糖浓度弱相关（p<0.09）。与野生型等位基因携带者相比，罕见的纯合子在负荷后120分钟的葡萄糖浓度增加（p≤0.05）。单倍型分析显示与糖尿病风险显著相关（p=0.04），并证实了单SNP分析。总之，我们重复了我们以前的发现，并发现SREBF 1c基因5′区的SNP与2型糖尿病风险和血糖浓度相关的证据。
The sterol regulatory element-binding factor (SREBF)-1c is a transcription factor involved in the regulation of lipid and glucose metabolism. We have previously found evidence that a common SREBF1c single-nucleotide polymorphism (SNP), located between exons 18c and 19c, is associated with an increased risk of type 2 diabetes. The present study aimed to replicate our previously reported association in a larger case–control study and to examine an additional five SREBF1c SNPs for their association with diabetes risk and plasma glucose concentrations. We genotyped six SREBF1c SNPs in two case–control studies (n=1,938) and in a large cohort study (n=1,721) and tested for association with type 2 diabetes and with plasma glucose concentrations (fasting and 120-min post-glucose load), respectively. In the case–control studies, carriers of the minor allele of the previously reported SNP (rs11868035) had a significantly increased diabetes risk (odds ratio [OR]=1.20 [95% CI 1.04–1.38], p=0.015). Also, three other SNPs (rs2236513, rs6502618 and rs1889018), located in the 5′ region, were significantly associated with diabetes risk (OR ≥1.21, p≤0.006). Furthermore, two SNPs (rs2236513 and rs1889018) in the 5′ region were weakly (p<0.09) associated with plasma glucose concentrations in the cohort study. Rare homozygotes had increased (p≤0.05) 120-min post-load glucose concentrations compared with carriers of the wild-type allele. Haplotype analyses showed significant (p=0.04) association with diabetes risk and confirmed the single SNP analyses. In summary, we replicated our previous finding and found evidence for SNPs in the 5′ region of the SREBF1c gene to be associated with the risk of type 2 diabetes and plasma glucose concentration.
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