High levels of inflammatory biomarkers are associated with increased allele-specific apolipoprotein(a) levels in African-Americans
High levels of inflammatory biomarkers are associated with increased allele-specific apolipoprotein(a) levels in African-Americans
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DOI：
10.1210/jc.2007-2416
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发表时间：
2008-04-01
影响因子：
5.8
通讯作者：
Berglund, Lars
中科院分区：
文献类型：
--
作者：
Anuurad, Erdembileg;Rubin, Jill;Berglund, Lars
背景：炎症在心血管疾病（CVD）中的作用已经确立。脂蛋白(a) [Lp(a)]是一种独立的心血管疾病危险因素，其血浆水平由载脂蛋白(a)[载脂蛋白(a)]基因决定，载脂蛋白(a)含有炎症反应因子。设计：我们研究了炎症对非裔美国人和白种人等位基因特异性载脂蛋白(a)水平的影响。我们测定了167名非裔美国人和259名白种人的Lp(a)水平、载脂蛋白(a)大小、等位基因特异性载脂蛋白(a)水平、纤维蛋白原和c反应蛋白（CRP）水平。结果：非裔美国人的Lp(a)水平升高，CRP水平< 3 vs. >= 3mg /l (143 vs. 108 nmol/l), P = 0.009]或纤维蛋白原水平< 340 vs. >= 340 mg/l, P = 0.002。接下来，我们分析了不同载脂蛋白大小的等位基因特异性载脂蛋白(a)水平。等位基因特异性载脂蛋白(a)水平在CRP或纤维蛋白原组中在小载脂蛋白(a)大小（< 22 kringle 4重复）的非裔美国人或白种人中没有差异。中等apo(a)大小（22-30 kringle 4重复）的等位基因特异性apo(a)水平在非裔美国人中明显更高，CRP或纤维蛋白原水平高的人比低水平的人（88比67 nmol/l， P = 0.014, 91比59 nmol/l， P < 0.0001）。在白种人中没有发现差异。结论：在非裔美国人中，CRP或纤维蛋白原水平升高与等位基因特异性中等载脂蛋白(a)水平升高有关，而在白种人中则无此关系。这些发现表明，促炎条件导致非裔美国人中等载脂蛋白(a)水平选择性增加，并表明炎症相关事件可能导致非裔美国人和白种人之间Lp(a)水平的种族差异。
Background: A role of inflammation for cardiovascular disease (CVD) is established. Lipoprotein(a) [Lp(a)] is an independent CVD risk factor where plasma levels are determined by the apolipoprotein(a) [apo(a)] gene, which contains inflammatory response elements.Design: We investigated the effect of inflammation on allele-specific apo(a) levels in African-Americans and Caucasians. We determined Lp(a) levels, apo(a) sizes, allele-specific apo(a) levels, fibrinogen and C-reactive protein (CRP) levels in 167 African-Americans and 259 Caucasians.Results: Lp(a) levels were increased among African-Americans with higher vs. lower levels of CRP [< 3 vs. >= 3 mg/liter (143 vs. 108 nmol/liter), P = 0.009] or fibrinogen (< 340 vs. >= 340 mg/liter, P = 0.002). We next analyzed allele-specific apo(a) levels for different apo( a) sizes. No differences in allele-specific apo(a) levels across CRP or fibrinogen groups were seen among African-Americans or Caucasians for small apo(a) sizes (< 22 kringle 4 repeats). Allele-specific apo(a) levels for medium apo(a) sizes (22-30 kringle 4 repeats) were significantly higher among African-Americans, with high levels of CRP or fibrinogen compared with those with low levels (88 vs. 67 nmol/liter, P = 0.014, and 91 vs. 59 nmol/liter, P < 0.0001, respectively). No difference was found for Caucasians.Conclusions: Increased levels of CRP or fibrinogen are associated with higher allele-specific medium-sized apo(a) levels in African-Americans but not in Caucasians. These findings indicate that proinflammatory conditions result in a selective increase in medium-sized apo(a) levels in African-Americans and suggest that inflammation-associated events may contribute to the interethnic difference in Lp(a) levels between African-Americans and Caucasians.