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KIF6、LPA、TAS2R50 和 VAMP8 基因变异、普伐他汀降低低密度脂蛋白胆固醇的反应与老年人心脏病风险降低的关系。

KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly.

机构信息

Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA.

出版信息

Atherosclerosis. 2012 Feb;220(2):456-62. doi: 10.1016/j.atherosclerosis.2011.11.037. Epub 2011 Dec 7.


DOI:10.1016/j.atherosclerosis.2011.11.037
PMID:22192511
Abstract

Single nucleotide polymorphisms (SNPs) at the KIF6 (kinesin like protein 6, rs20455 or 719Arg), LPA (lipoprotein(a), rs3798220), TAS2R50 (taste receptor type 2, member 50, rs1376251) and VAMP8 (vesicle-associated membrane protein 8, rs1010) have previously been associated with low density lipoprotein cholesterol (LDL-C) lowering response to statins, coronary heart disease (CHD) at baseline, or CHD events on trial. We examined SNPs at the KIF6 (rs20455 or 719Arg), LPA (rs3798220), TAS2R50 (rs1376251) and VAMP8 (rs1010) in 5,411 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and were followed for a mean of 3.2 years. No SNP was related to vascular disease at baseline. Only the KIF6 SNP was related to LDL-C lowering with homozygous Arg 719 subjects being significantly less responsive than other groups (p=0.025, -34.2 vs. -36.1%). With regard to the primary CHD endpoint on trial (fatal or non-fatal myocardial infarction or stroke), we observed a significant relationship for KIF6 719Arg homozygotes (p=0.03, hazards ratio 0.47, 12.8% of the population) in women on pravastatin only, and for TAS2R50 for the AA genotype (p=0.03, hazards ratio 1.76, 8.9% of the population), also only in women on pravastatin. Our data indicate that the assessment of KIF6 rs20455 and TAS2R50 rs1376251 genotypes are not useful for predicting statin induced cardiovascular risk reduction in men, but do predict CHD risk reduction in women in this elderly population. However, these differences are no longer significant after correction for multiple comparisons, and we do not recommend the assessment of any of these SNPs in clinical practice.

摘要

单核苷酸多态性(SNPs)位于 KIF6(驱动蛋白样蛋白 6,rs20455 或 719Arg)、LPA(脂蛋白(a),rs3798220)、TAS2R50(味觉受体 2 型,成员 50,rs1376251)和 VAMP8(囊泡相关膜蛋白 8,rs1010),先前与他汀类药物降低低密度脂蛋白胆固醇(LDL-C)反应、基线时冠心病(CHD)或试验中的 CHD 事件相关。我们在 PROSPER(高危老年人普伐他汀前瞻性研究)中检查了 KIF6(rs20455 或 719Arg)、LPA(rs3798220)、TAS2R50(rs1376251)和 VAMP8(rs1010)的 SNPs,5411 名参与者平均年龄为 75.3 岁,他们被随机分配到普伐他汀 40mg/天或安慰剂组,平均随访 3.2 年。没有 SNP 与基线时的血管疾病相关。只有 KIF6 SNP 与 LDL-C 降低相关,纯合子 Arg719 受试者的反应明显低于其他组(p=0.025,-34.2%与-36.1%)。关于试验中的主要 CHD 终点(致命或非致命性心肌梗死或中风),我们仅在服用普伐他汀的女性中观察到 KIF6 719Arg 纯合子的显著关系(p=0.03,风险比 0.47,人群的 12.8%),以及仅在服用普伐他汀的女性中观察到 TAS2R50 的 AA 基因型(p=0.03,风险比 1.76,人群的 8.9%)。我们的数据表明,评估 KIF6 rs20455 和 TAS2R50 rs1376251 基因型对于预测男性他汀类药物引起的心血管风险降低并不有用,但在该老年人群中,对于女性,可以预测 CHD 风险降低。然而,在进行多次比较校正后,这些差异不再显著,我们不建议在临床实践中评估这些 SNP 中的任何一个。

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[8]
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[9]
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[10]
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