Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination
Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination
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DOI：
10.1038/sj.gene.6364434
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发表时间：
2007-12-01
影响因子：
5
通讯作者：
Arnett, D. K.
中科院分区：
文献类型：
--
作者：
Bielinski, S. J.;Pankow, J. S.;Arnett, D. K.
动脉粥样硬化是一种慢性炎症过程。在炎症过程中起关键作用的是单核细胞趋化蛋白-1（MCP-1）。为了定位影响循环MCP-1水平的基因组区域，在白人和黑人样本中进行了全基因组连锁扫描。在国家心肺血液研究所家庭心脏研究的随访检查中，2501名白色和513名黑人参与者的表型和遗传标记数据可用。在调整性别、年龄、年龄-性别相互作用、吸烟状况、终生吸烟暴露（包-年）和场中心的影响后，MCP-1的遗传度在白人中为0.37，在黑人中为0.47。在3号染色体上的黑人和白色样本中观察到MCP-1的显著连锁（在78 cM处比值比（LOD）的对数= 3.5，P = 0.0001），并且在5号染色体上的白人中观察到暗示性连锁（在128 cM处LOD= 1.8，P= 0.002）。位于3号染色体上的连锁峰下的是趋化因子受体基因簇，包括MCP-1的受体CCR 2。这项研究提供了初步证据，将受体的遗传变异与其配体的循环水平联系起来，正如先前对低密度脂蛋白受体所证明的那样。需要进一步表征这些染色体区域以鉴定与MCP-1循环水平相关的功能突变。
Atherogenesis is a chronic inflammatory process. Critical in the inflammation process is monocyte chemoattractant protein-1 (MCP-1). To locate genomic regions that affect circulating MCP-1 levels, a genome-wide linkage scan was conducted in a sample of whites and blacks. Phenotype and genetic marker data were available for 2501 white and 513 black participants in the National Heart Lung Blood Institute Family Heart Study follow-up examination. Heritability for MCP-1 was 0.37 in whites and 0.47 in blacks after adjusting for the effects of sex, age, age-sex interaction, smoking status, lifetime smoking exposure (pack-years) and field center. Significant linkage was observed for MCP-1 in a combined black and white sample on chromosome 3 (logarithm of the odds ratio (LOD) = 3.5 at 78 cM, P = 0.0001) and suggestive linkage was observed in whites on chromosome 5 (LOD= 1.8 at 128 cM, P= 0.002). Located under the linkage peak on chromosome 3 is the chemokine receptor gene cluster, including CCR2, the receptor for MCP-1. This study provides preliminary evidence linking genetic variation in a receptor to circulating levels of its ligand, as previously demonstrated for the low-density lipoprotein receptor. Further characterization of these chromosomal regions is needed to identify the functional mutations associated with circulating levels of MCP-1.