The expression of type III hyperlipoproteinemia: involvement of lipolysis genes
The expression of type III hyperlipoproteinemia: involvement of lipolysis genes
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DOI：
10.1038/ejhg.2008.202
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发表时间：
2009-05-01
影响因子：
5.2
通讯作者：
Smelt, Augustinus H. M.
中科院分区：
文献类型：
--
作者：
Henneman, Peter;van der Sman-de Beer, Femke;Smelt, Augustinus H. M.
III型高脂蛋白血症（HLP）主要见于纯合子载脂蛋白（APO） E2 （R158C）携带者。通过检测APOC3、APOA5、HL（肝脂肪酶）和LPL（脂蛋白脂肪酶）基因的多态性，研究了113例高脂血症和52例降脂症E2/2患者中III型HLP表达的遗传因素。此外，188例正常血脂荷兰对照组（NDCP）和141例高甘油三酯血症（HTG）患者也进行了基因分型。4个HL基因多态性和2个LPL基因多态性与III型HLP无相关性。III型HLP患者APOC3 3238 G > C和APOA5 - 1131 T > C罕见等位基因（连锁不平衡）的频率显著高于正常血脂E2/2组，分别为15.6比6.9%和15.1比5.8%，差异有统计学意义（P < 0.05）。此外，APOA5 c.56的频率g> C多态性与LPL关系研究[j]gbbbba突变在III型HLP患者中较高，但不显著。约58%的III型HLP患者携带APOA5 - 1131t> C, C .56G > C和/或LPL C .27与27%的正常血脂APOE2/2受试者相比（优势比3.7,95%置信区间= 1.8-7.5,P < 0.0001）。HTG患者APOA5、APOC3和LPL多态性的等位基因频率相似，而NDCP患者的等位基因频率与正常血脂的APOE2/2相似。apo3 3238 G > C/APOA5 - 1131 T > C多态性的患者比没有这种多态性的患者表现出更严重的高血脂。脂解基因多态性与APOE2/2中III型HLP的表达和严重程度相关。
Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G > C and APOA5 - 1131 T > C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P < 0.05). Furthermore, the frequencies of the APOA5 c.56 G > C polymorphism and LPL c.27 G > A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 - 1131 T > C, c.56 G > C and/or LPL c.27 G > A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval = 1.8-7.5, P < 0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G > C/APOA5 - 1131 T > C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.