Different genes and polymorphisms affecting high-density lipoprotein cholesterol levels in Greek familial hypercholesterolemia patients
Different genes and polymorphisms affecting high-density lipoprotein cholesterol levels in Greek familial hypercholesterolemia patients
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DOI：
10.1089/gte.2006.10.192
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发表时间：
2006-09-01
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影响因子：
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通讯作者：
Visvikis-Siest, Sophie
中科院分区：
文献类型：
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作者：
Dedoussis, George V. Z.;Maumus, Sandy;Visvikis-Siest, Sophie
家族性高胆固醇血症（FH）是一种以高低密度脂蛋白胆固醇（LDL-C）浓度为特征的遗传性疾病，其经常引起过早的冠状动脉疾病。FH的临床表达是高度可变的，即使在携带相同LDL受体基因突变的患者中也是如此。这种变化可能是由于环境和其他遗传因素。我们研究了84例FH患者APOC Ⅲ T1100 C、FV Gln 506 Arg、ADRB 2 Glu 27 Gln、SELE Ser 128 Arg、SELE Leu 554 Phe和ENaCa Ala 663 Thr多态性对HDL-C变异的影响。对于ApoCIII T1100 C，TT基因型受试者的HDL-C水平高于其他基因型组（p = 0.046）。类似地，在ADRB 2 27 Glu/Gln杂合子和ADRB 2 27 Gln/Gln纯合子中Gln等位基因的存在与较高的HDL-C水平相关（p = 0.014）。在检测的其他多态性中，没有一个与HDL-C水平的变化相关。在调整年龄和性别后，用线性回归分析评估每个多态性对血脂浓度的影响。研究的变量包括总胆固醇、LDL-C、高密度脂蛋白（HDL）-C、甘油三酯、载脂蛋白A（Apo-A）和B（ApoB）以及脂蛋白α在应用ApoCIII T1100 C、FV Gln 506 Arg和ADRB 2 Glu 27 Gln多态性的模型中，LP α、HDL-C浓度显著不同（分别为p = 0.01，p = 0.018，p = 0.04）。这些结果表明，高密度脂蛋白胆固醇水平在FH杂合子可能受到几种不同的遗传变异。
Familial Hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol (LDL-C) concentrations that frequently gives rise to premature coronary artery disease. The clinical expression of FH is highly variable, even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. We investigated the effect of APOCIII T1100C, FV Gln506Arg, ADRB2 Glu27Gln, SELE Ser128Arg, SELE Leu554Phe, and ENaCa Ala663Thr polymorphisms on the HDL-C variations in 84 patients with FH. For ApoCIII T1100C, subjects with the TT genotype presented higher HDL-C levels than the other genotype groups (p = 0.046). Similarly the presence of the Gln allele in ADRB2 27 Glu/Gln heterozygotes and ADRB2 27 Gln/Gln homozygotes was associated with higher HDL-C levels (p = 0.014). Among the other polymorphisms tested, none of them were associated with variations in HDL-C levels. The influence of each polymorphism on lipid concentrations was evaluated with linear regression analyses after adjustment for age and sex. Among the variables studied including total cholesterol, LDL-C, high-density lipoprotein (HDL)-C, triglycerides, apolipoprotein A (Apo-A) and B ( ApoB), and lipoprotein alpha (LP alpha), HDL-C concentration was significantly different in models applied for polymorphisms ApoCIII T1100C, FV Gln506Arg, and ADRB2 Glu27Gln (p = 0.01, p = 0.018, p = 0.04, respectively). These results suggest that HDL-C levels in FH heterozygotes may be affected by several different genetic variants.