Berthier Marie-Thérèse, Houde Alain, Bergeron Jean, Prud'homme Denis, Després Jean-Pierre, Vohl Marie-Claude
Lipid Research Center, CHUQ Pavilion CHUL, 2705 Laurier Blvd, TR93, Sainte-Foy, Quebec, G1V 4G2, Canada.
J Hum Genet. 2003;48(7):367-73. doi: 10.1007/s10038-003-0039-x. Epub 2003 Jul 8.
An atherogenic dyslipidemia, characterized by increased plasma triglyceride and apolipoprotein (apo) B levels, low HDL-cholesterol concentrations and the development of small, dense LDL particles has been associated with the presence of abdominal-visceral obesity. Visceral obesity is also associated with a hypercoagulate state and elevated concentrations of procoagulant factors such as factor VII. Moreover, it is known that some genetic variants in the gene encoding factor VII alter its activity and concentration, and consequently these variants may have an impact on atherosclerosis development. The objective of this study was to verify whether the factor VII R353Q polymorphism contributes to predict the risk of an atherogenic dyslipidemia in absence and in the presence of visceral obesity. A sample of 299 French-Canadian men, selected in order to cover a wide range of body fatness values, participated in this study. We observed that the R353 allele was more commonly observed among men characterized by apo B levels below 1.09 g/l than among men with apo B levels greater or above this threshold value (allele frequency of 92.1 vs 85.4%, chi(2)=6.18, P=0.01). Multivariate analyses further showed that the genotype R353/R353 was associated with a lower risk to exhibit atherogenic concentrations of total-apo B (>/=1.09 g/l) and LDL apo B (>/=0.95 g/l) before (odds ratio:0.47, 95%CI=0.27-0.90, P=0.02; odds ratio:0.46, 95%CI=0.25-0.85, P=0.01, respectively) and after adjustments for age and visceral AT (odds ratio:0.49, 95%CI=0.24-0.91, P=0.02; odds ratio:0.44, 95%CI=0.23-0.85, P=0.01, respectively). When the two genotype groups were further divided on the basis of visceral adipose tissue (AT) accumulation using a cutoff point of 130 cm(2), we observed that R353/R353 homozygotes with low visceral AT were characterized by a more favorable lipoprotein-lipid profile, mainly lower total-cholesterol, total-apo B, and LDL-apo B levels compared with R353/R353 homozygotes with high levels of visceral AT. In contrast, irrespective of obesity, plasma lipid levels among carriers of the Q353 allele were similar to those of viscerally obese men homozygous for the R353 allele. In conclusion, results of the present study suggest that the factor VII R353 allele is associated with lower concentrations of plasma apo B levels. However, the presence of visceral obesity abolishes this effect. Further studies will be necessary to confirm this association and the mechanism involved.
一种致动脉粥样硬化性血脂异常，其特征为血浆甘油三酯和载脂蛋白（apo）B水平升高、高密度脂蛋白胆固醇浓度降低以及小而密的低密度脂蛋白颗粒的出现，与腹内脏器肥胖有关。内脏肥胖还与高凝状态以及促凝血因子如因子VII浓度升高有关。此外，已知编码因子VII的基因中的一些基因变异会改变其活性和浓度，因此这些变异可能对动脉粥样硬化的发展产生影响。本研究的目的是验证因子VII R353Q多态性是否有助于预测在无内脏肥胖和有内脏肥胖情况下发生致动脉粥样硬化性血脂异常的风险。选取了299名法裔加拿大男性样本，以涵盖广泛的体脂值范围，参与了本研究。我们观察到，在apo B水平低于1. 将两个基因型组根据内脏脂肪组织（AT）积累情况进一步以130 cm²的截断点进行划分时，我们观察到内脏AT水平低的R353/R353纯合子的脂蛋白-脂质谱更有利，与内脏AT水平高的R353/R353纯合子相比，主要是总胆固醇、总apo B和LDL-apo B水平更低。相比之下，无论肥胖情况如何，Q353等位基因携带者的血浆脂质水平与R353等位基因纯合的内脏肥胖男性相似。总之，本研究结果表明因子VII R353等位基因与较低的血浆apo B水平浓度相关。然而，内脏肥胖的存在消除了这种效应。需要进一步研究来证实这种关联及其涉及的机制。 09 g/l的男性中，R353等位基因比apo B水平高于此阈值的男性中更常见（等位基因频率分别为92.1%和85.4%，χ² = 6.18，P = 0.01）。多变量分析进一步表明，基因型R353/R353与在调整年龄和内脏AT之前（优势比：0.47，95%置信区间 = 0.27 - 0.90，P = 0.02；优势比：0.46，95%置信区间 = 0.25 - 0.85，P = 0.01）和之后出现致动脉粥样硬化性总apo B（≥1.09 g/l）和LDL apo B（≥0.95 g/l）浓度的较低风险相关（优势比：0.49，95%置信区间 = 0.24 - 0.91，P = 0.02；优势比：0.44，95%置信区间 = 0.23 - 0.85，P = 0.01）。
