Heidemann Britt E, Visseren Frank Lj, van Setten Jessica, Marais A David, Koopal Charlotte
Department of Vascular Medicine.
Department of Cardiology, University Medical Center Utrecht, Utrecht University, The Netherlands.
Cardiovasc Endocrinol Metab. 2023 Jan 18;12(1):e0278. doi: 10.1097/XCE.0000000000000278. eCollection 2023 Mar.
Clearance of triglyceride-rich lipoproteins (TRLs) is mediated by several receptors, including heparan sulfate proteoglycans (HSPGs). Sulfate glucosamine-6-O-endosulfatase-2 is a gene related to the regulation of HSPG. A variant in this gene, rs2281279, has been shown to be associated with triglycerides and insulin resistance.
To determine the relationship between rs2281279, metabolic parameters and vascular events, and type 2 diabetes mellitus (T2DM) in patients at high cardiovascular risk and whether genotype modifies this relationship.
Patients ( = 4386) at high cardiovascular risk from the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease study were stratified according to their imputed rs2281279 genotype: AA ( = 2438), AG ( = 1642) and GG ( = 306). Effects of rs2281279 on metabolic parameters, vascular events and T2DM were analyzed with linear regression and Cox models.
There was no relationship between imputed rs2281279 genotype and triglycerides, non-high-density lipoprotein (HDL)-cholesterol, insulin and quantitative insulin sensitivity check index. During a median follow-up of 11.8 (IQR, 9.3-15.5) years, 1026 cardiovascular events and 320 limb events occurred. The presence of the G allele in rs2281279 did not affect the risk of vascular events [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.94-1.14] or limb events (HR, 0.92; 95% CI, 0.77-1.10). The presence of the G allele in rs2281279 did not affect the risk of T2DM (HR, 1.09; 95% CI, 0.94-1.27). The presence of the minor G allele of rs2281279 was associated with a beneficial risk profile in ε2ε2 patients, but not in ε3ε3 patients.
Imputed rs2281279 genotype is not associated with metabolic parameters and does not increase the risk of vascular events or T2DM in patients at high risk for cardiovascular disease.
富含甘油三酯的脂蛋白（TRLs）的清除由包括硫酸乙酰肝素蛋白聚糖（HSPGs）在内的多种受体介导。硫酸氨基葡萄糖-6-O-内硫酸酯酶-2是一个与HSPG调节相关的基因。该基因中的一个变体rs2281279已被证明与甘油三酯和胰岛素抵抗有关。
确定rs2281279、代谢参数与血管事件以及心血管疾病高风险患者的2型糖尿病（T2DM）之间的关系，以及基因型是否会改变这种关系。
根据乌得勒支心血管队列-动脉疾病的第二次表现研究中推算的rs2281279基因型，将4386名心血管疾病高风险患者进行分层：AA（n = 2438）、AG（n = 1642）和GG（n = 306）。使用线性回归和Cox模型分析rs2281279对代谢参数、血管事件和T2DM的影响。
推算的rs2281279基因型与甘油三酯、非高密度脂蛋白（HDL）胆固醇、胰岛素和定量胰岛素敏感性检查指数之间没有关系。在中位随访11.8（四分位间距，9.3 - 15.5）年期间，发生了1026例心血管事件和320例肢体事件。rs2281279中G等位基因的存在不影响血管事件风险[风险比（HR），1.03；95%置信区间（CI），0.94 - 1.14]或肢体事件风险（HR，0.92；95% CI，0.77 - 1.10）。rs2281279中G等位基因的存在不影响T2DM风险（HR，1.09；95% CI，0.94 - 1.27）。rs2281279的次要G等位基因的存在与ε2ε2患者的有益风险特征相关，但在ε3ε3患者中并非如此。
推算的rs228l279基因型与代谢参数无关，也不会增加心血管疾病高风险患者的血管事件或T2DM风险。
