高胆固醇血症患者枯草溶菌素转化酶9基因突变研究
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河北省科技厅科技支撑项目(10276105D-57)


Research of Gene Mutation of Proprotein Convertase Subtilisin/Kexin 9 in Hypercholesterolemia
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    摘要:

    目的探讨国人单纯性高胆固醇血症患者人类枯草溶菌素转化酶9基因突变情况。方法排除载脂蛋白B100基因Q3500R位点突变及低密度脂蛋白受体基因突变后的100例单纯性高胆固醇血症患者,提取其基因组DNA,采用聚合酶链反应方法扩增枯草溶菌素转化酶9基因的12个外显子,进行DNA测序分析,同时选100例健康人群作为对照。结果100例高胆固醇血症患者中,6例发现3处错义突变(D320N、V312F、R319E)、1处框移突变(934delGV312S)、3处同义突变(A305A、Q342Q、K125K)和1处剪接点突变(第2内含子5′剪接位点突变)。结论枯草溶菌素转化酶9基因在以上位点发生的突变可引起单纯性高胆固醇血症。枯草溶菌素转化酶9基因突变可能与国人高胆固醇血症有关。

    Abstract:

    AimTo investigate proprotein convertase subtilisin/kexin 9 (PCSK9) gene mutations in Chinese with hypercholesterolemia.MethodsGenomic DNA was extracted from 100 cases of hypercholesterolemia and 100 healthy normal individuals with age and sex matched.Apolipoprotein B100 (Apo B100) and low density lipoprotein receptor (LDLR) mutations were excluded.All of the 12 exons of PCSK9 gene were amplified by polymerase chain reaction (PCR).The PCR products were sequenced directly.ResultsThree missense mutation (D320N, V312F and R319E), one frameshift mutation (934delGV312S), three samesense mutation (A305A, Q342Q, K125K) and one splice junction mutation (5′ splice junction site mutation in intron 2) were found in PCSK9 gene in six patients among 100 patients.ConclusionThe mutations of PCSK9 gene are maybe one reason to cause Chinese hypercholesterolemia.

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宋光耀,张明明,孙海娟,王俊明,帖彦清,郝志华,马倩.高胆固醇血症患者枯草溶菌素转化酶9基因突变研究[J].中国动脉硬化杂志,2012,20(8):731~735.

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  • 收稿日期:2010-08-26
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