sul2基因基因变异、代谢参数与心血管高危患者血管疾病之间的关系

IF 1.3 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Endocrinology & Metabolism Pub Date : 2023-03-01 DOI:10.1097/XCE.0000000000000278
Britt E Heidemann, Frank Lj Visseren, Jessica van Setten, A David Marais, Charlotte Koopal
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引用次数: 0

摘要

富含甘油三酯的脂蛋白(TRLs)的清除是由几种受体介导的,包括硫酸肝素蛋白聚糖(HSPGs)。硫酸氨基葡萄糖-6- o -氨基硫酸酯酶-2是一个与HSPG调控相关的基因。该基因的一个变体rs2281279已被证明与甘油三酯和胰岛素抵抗有关。目的:探讨rs2281279、代谢参数和血管事件与心血管高危患者2型糖尿病(T2DM)的关系,以及APOE基因型是否改变了这种关系。方法:根据输入的rs2281279基因型对乌得勒支心血管队列-动脉疾病第二表现研究中的高危心血管患者(n = 4386)进行分层:AA (n = 2438)、AG (n = 1642)和GG (n = 306)。采用线性回归和Cox模型分析rs2281279对代谢参数、血管事件和T2DM的影响。结果:rs2281279基因型与甘油三酯、非高密度脂蛋白(HDL)-胆固醇、胰岛素及胰岛素定量敏感性检查指标均无相关性。在中位随访11.8 (IQR, 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的风险[危险比(HR), 1.03;95%可信区间(CI), 0.94-1.14]或肢体事件(HR, 0.92;95% ci, 0.77-1.10)。rs2281279中G等位基因的存在对T2DM的风险没有影响(HR, 1.09;95% ci, 0.94-1.27)。rs2281279小等位基因G的存在与ε2ε2患者的有益风险相关,但与ε3ε3患者无关。结论:rs2281279基因型与代谢参数无关,不会增加心血管疾病高危患者发生血管事件或T2DM的风险。
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The association between a genetic variant in the SULF2 gene, metabolic parameters and vascular disease in patients at high cardiovascular risk.

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.

Objective: 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 APOE genotype modifies this relationship.

Methods: Patients (n = 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 (n = 2438), AG (n = 1642) and GG (n = 306). Effects of rs2281279 on metabolic parameters, vascular events and T2DM were analyzed with linear regression and Cox models.

Results: 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.

Conclusions: 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.

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来源期刊
Cardiovascular Endocrinology & Metabolism
Cardiovascular Endocrinology & Metabolism CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
5.60
自引率
0.00%
发文量
24
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