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亚洲印度人群中载脂蛋白(a)大小多态性分析:与脂蛋白(a)浓度及冠心病的关联

Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease.

作者信息

Geethanjali F S, Luthra Kalpana, Lingenhel Arno, Kanagasaba-Pathy A S, Jacob Jose, Srivastava Lalit M, Vasisht Suman, Kraft Hans-Georg, Utermann Gerd

机构信息

Institute of Medical Biology and Human Genetics, University of Innsbruck, 6020 Innsbruck, Austria.

出版信息

Atherosclerosis. 2003 Jul;169(1):121-30. doi: 10.1016/s0021-9150(03)00143-6.

DOI:10.1016/s0021-9150(03)00143-6
PMID:12860258
Abstract

Most studies aiming to detect associations of genetic variation with common complex diseases, e.g. coronary heart disease (CHD) have been performed in populations with a western lifestyle but it is unclear whether associations detected in one geographic group exist also in others. We here have determined lipoprotein(a) levels and apo(a) K-IV-2 repeat genotypes in CHD patients (N=254) and controls (N=480) from two Asian Indian populations (Tamil Nadu and New Delhi). In both populations and also in the pooled dataset median Lp(a) levels were significantly elevated in the patients (27.4 mg/dl) compared with the controls (17.6 mg/dl). Apo(a) K-IV-2 allele frequencies were not different between the CHD patients and controls and thus did not explain the increased Lp(a) levels in CHD patients. Contrary to what has recently been observed in Black and White men short (K-IV<or=22) alleles associated with high Lp(a) concentration were not overrepresented in the patients. Rather, short (K-IV<or=22), intermediate (K-IV 23-29) and long (K-IV>or=30) apo(a) alleles were all associated with higher Lp(a) levels in the patients. Accordingly relative risk (estimated as odds ratio) for CHD rose continuously with increasing Lp(a) but was independent of apo(a) allele length. Together with previous studies our results indicate that the relation between apo(a) genotypes, Lp(a) levels, and CHD may be heterogeneous across ethnic groups and that it depends on the genetic architecture of the Lp(a) trait in a given population whether an association of K-IV-2 repeat length with CHD exists or not.

摘要

大多数旨在检测基因变异与常见复杂疾病(如冠心病)之间关联的研究都是在具有西方生活方式的人群中进行的,但尚不清楚在一个地理群体中检测到的关联是否也存在于其他群体中。我们在此测定了来自两个亚洲印度人群体(泰米尔纳德邦和新德里)的冠心病患者(N = 254)和对照组(N = 480)的脂蛋白(a)水平和载脂蛋白(a) K-IV-2重复基因型。在这两个人群体以及合并的数据集中,患者的脂蛋白(a)水平中位数(27.4 mg/dl)与对照组(17.6 mg/dl)相比均显著升高。冠心病患者和对照组之间的载脂蛋白(a) K-IV-2等位基因频率没有差异,因此不能解释冠心病患者脂蛋白(a)水平的升高。与最近在黑人和白人男性中观察到的情况相反,与高脂蛋白(a)浓度相关的短(K-IV≤22)等位基因在患者中并未过度出现。相反,短(K-IV≤22)、中等(K-IV 23 - 29)和长(K-IV≥30)载脂蛋白(a)等位基因在患者中均与较高的脂蛋白(a)水平相关。因此,冠心病的相对风险(以比值比估计)随着脂蛋白(a)的升高而持续上升,但与载脂蛋白(a)等位基因长度无关。与先前的研究一起,我们的结果表明,载脂蛋白(a)基因型、脂蛋白(a)水平和冠心病之间的关系在不同种族群体中可能是异质的,并且在给定人群中,K-IV-2重复长度与冠心病之间是否存在关联取决于脂蛋白(a)性状的遗传结构。

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