ABCB1基因C3435T多态性对他汀类药物降脂疗效影响的Meta分析
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篇名: ABCB1基因C3435T多态性对他汀类药物降脂疗效影响的Meta分析
TITLE: Effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins:a meta-analysis
摘要: 目的 系统评价ABCB1基因C3435T多态性对他汀类药物降脂疗效的影响。方法计算机检索PubMed、WebofScience、theCochraneLibrary、中国知网和维普网,收集患者使用他汀类药物的队列研究,检索时限为建库至2023年11月1日。筛选文献、提取数据、评价质量后,采用RevMan5.4软件进行Meta分析。结果共纳入11项文献,共计1575例患者。Meta分析结果显示,显性遗传模型下,CT+TT型患者的低密度脂蛋白胆固醇(LDL-C)降低程度[MD=-1.87,95%CI(-3.62,-0.13),P=0.04]、总胆固醇(TC)降低程度[MD=-1.42,95%CI(-2.80,-0.04),P=0.04]均显著高于CC型;CT+TT型患者的高密度脂蛋白胆固醇(HDL-C)升高程度[MD=-0.65,95%CI(-2.48,1.18),P=0.49]、甘油三酯(TG)降低程度[MD=-0.05,95%CI(-2.94,2.84),P=0.97]与CC型比较,差异均无统计学意义。隐性遗传模型下,TT型患者的TC降低程度[MD=2.26,95%CI(0.97,3.56),P=0.0006]、HDL-C升高程度[MD=2.38,95%CI(0.42,4.35),P=0.02]均显著高于CC+CT型;CC+CT型患者的LDL-C降低程度[MD=1.53,95%CI(-0.10,3.15),P=0.07]、TG降低程度[MD=0.06,95%CI(-2.98,3.10),P=0.97]与TT型比较,差异均无统计学意义。加性遗传模型下,TT型患者的TC降低程度[MD=2.98,95%CI(1.27,4.69),P=0.0006]、LDL-C降低程度[MD=2.84,95%CI(0.67,5.01),P=0.01]均显著高于CC型;TT型患者的HDL-C升高程度[MD=2.40,95%CI(-0.17,4.97),P=0.07]、TG降低程度[MD=0.97,95%CI(-2.93,4.87),P=0.63]与CC型比较,差异均无统计学意义。结论血脂异常患者接受他汀类药物治疗时,LDL-C、TC降低效果可能与ABCB1基因C3435T杂合和纯合突变有关,即与CC型患者比较,CT或TT型患者的LDL-C、TC降低效果可能更明显;HDL-C升高效果可能与纯合突变有关,即与CC+CT型患者比较,TT型患者的HDL-C升高效果可能更明显;而TG变化可能与ABCB1基因C3435T多态性无关。
ABSTRACT: OBJECTIVE To systematically evaluate the effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins. METHODS Retrieved from PubMed, Web of Science, the Cochrane Library, CNKI and VIP, the cohort studies on the use of statins were collected from the inception to November 1, 2023. After literature screening, data extraction and quality evaluation, meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 11 literature involving 1 575 patients were included. The results showed that under the dominant genetic model, the reduction of low-density lipoprotein cholesterol (LDL-C) [MD=-1.87, 95%CI (-3.62, -0.13), P=0.04], total cholesterol (TC) [MD=-1.42, 95%CI (-2.80, -0.04), P=0.04] in patients with CT+TT genotype was significantly higher than CC genotype. There was no significant difference in the increase of high-density lipoprotein cholesterol (HDL-C) [MD=-0.65, 95%CI (-2.48, 1.18), P=0.49] or the decrease of triglyceride (TG) [MD=-0.05, 95%CI (-2.94, 2.84), P=0.97] between patients with CT+TT genotype and CC genotype. Under the recessive genetic model, the reduction of TC [MD=2.26, 95%CI (0.97, 3.56), P=0.000 6] and the increase of HDL-C [MD=2.38, 95%CI (0.42, 4.35), P=0.02] in patients with TT genotype were significantly higher than CC+ CT genotype. There was no significant difference in the reduction of LDL-C [MD=1.53, 95%CI (-0.10, 3.15), P=0.07] or TG [MD=0.06, 95%CI (-2.98, 3.10), P=0.97] between CC+CT genotype and TT genotype. Under the additive genetic model, the reduction of TC [MD=2.98, 95%CI (1.27, 4.69), P=0.000 6] and LDL-C [MD=2.84, 95%CI (0.67, 5.01), P=0.01] in patients with TT genotype were significantly higher than CC genotype. There was no significant difference in the increase of HDL-C [MD=2.40, 95%CI (-0.17, 4.97), P=0.07] or the decrease of TG [MD=0.97, 95%CI    (-2.93, 4.87), P=0.63] between patients with TT genotype and CC genotype. CONCLUSIONS The reduction of LDL-C and TC in patients with dyslipidemia treated with statins may be related to the heterozygous and homozygous mutation of C3435T in ABCB1 gene, and the reduction of LDL-C and TC in patients with CT or TT genotype is more obvious, compared with patients with CC genotype. The elevation of HDL-C may be related to homozygous mutation, and the effect of HDL-C elevation may be more obvious in patients with TT genotype, compared with CC+CT genotype. However, the change of TG may not be related to the C3435T polymorphism in ABCB1 gene.
期刊: 2024年第35卷第08期
作者: 黄治果;李荣添;郭顺;李桂华;贾暖
AUTHORS: HUANG Zhiguo,LI Rongtian,GUO Shun,LI Guihua,JIA Nuan
关键字: 他汀类药物;ABCB1基因;C3435T多态性;降脂疗效;基因型
KEYWORDS: statins; ABCB1 gene; C3435T polymorphism; lipid-lowering efficacy; genotype
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