SULF2 strongly prediposes to fasting and postprandial triglycerides in patients with obesity and type 2 diabetes mellitus.
SULF2 strongly prediposes to fasting and postprandial triglycerides in patients with obesity and type 2 diabetes mellitus.
复制标题
DOI：
10.1002/oby.20682
复制
发表时间：
2014-05
期刊：
影响因子：
6.9
通讯作者：
Dallinga-Thie, Geesje M.
中科院分区：
文献类型：
--
作者：
Hassing, H. Carlijne;Surendran, R. Preethi;Derudas, Bruno;Verrijken, An;Francque, Sven M.;Mooij, Hans L.;Moens, Sophie J. Bernelot;' t Hart, Leen M.;Nijpels, Giel;Dekker, Jacqueline M.;Williams, Kevin Jon;Stroes, Erik S. G.;Van Gaal, Luc F.;Staels, Bart;Nieuwdorp, Max;Dallinga-Thie, Geesje M.
硫酸酯酶 2 (SULF2)（一种硫酸乙酰肝素重塑酶）的肝脏过度表达会强烈导致肥胖 2 型糖尿病 (T2DM) db/db 小鼠的甘油三酯 (TG) 水平升高。然而，缺乏人类数据。在这里，我们试图研究肥胖和/或 T2DM 患者肝脏 SULF2 表达和 SULF2 基因变异与 TG 代谢的关联。对 121 名肥胖受试者的肝活检进行了分析，以了解肝脏 SULF2 mRNA 水平与血浆 TG 之间的关系。在 210 名患有血脂异常的肥胖 T2DM 受试者中评估了 7 个 SULF2 tagSNP 与 TG 水平之间的关联。在 1316 名独立肥胖 T2DM 患者中重复了阳性结果。在按 SULF2 基因型分层的 29 名肥胖 T2DM 受试者中评估了餐后 TRL 清除率。在肥胖受试者中，肝脏 SULF2 表达与空腹血浆 TG 显着相关（r = 0.271；p = 0.003）。 SULF2 rs2281279(A>G) SNP 与肥胖 T2DM 受试者较低的空腹血浆 TG 水平重复相关 (p<0.05)。次要 G 等位基因的携带与较低水平的餐后血浆 TG (P<0.05) 和视黄酯 (RE) 水平 (P<0.001) 相关。这些发现表明 SULF2 是肥胖和 T2DM 引起的动脉粥样硬化性血脂异常的潜在治疗靶点。
Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodelling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here we sought to investigate the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM. Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; p=0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (p<0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P<0.05) and retinyl esters (RE) levels (P<0.001). These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM.
登录
查看更多内容
DOI：
10.1016/j.ecl.2006.06.002
发表时间：
2006-09-01
影响因子：
4.5
作者：
Chahil, Tina J.;Ginsberg, Henry N.
通讯作者：
Ginsberg, Henry N.
DOI：
10.1161/atvbaha.113.301637
发表时间：
2013-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Foley EM;Gordts PLSM;Stanford KI;Gonzales JC;Lawrence R;Stoddard N;Esko JD
通讯作者：
Esko JD
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
15.9
作者：
Fuki, IV;Kuhn, KM;Williams, KJ
通讯作者：
Williams, KJ
影响因子：
3.7
作者：
Matikainen N;Burza MA;Romeo S;Hakkarainen A;Adiels M;Folkersen L;Eriksson P;Lundbom N;Ehrenborg E;Orho-Melander M;Taskinen MR;Borén J
通讯作者：
Borén J