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.

中文翻译：

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循环 MCP-1 水平显示与 3 号染色体上的趋化因子受体基因簇存在关联：NHLBI 家族心脏研究随访检查。


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，对白人和黑人样本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随访检查中，有 2501 名白人和 513 名黑人参与者的表型和遗传标记数据可用。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）和现场中心的影响后，白人的 MCP-1 遗传力为 0.37，黑人的遗传力为 0.47。在 3 号染色体上的黑白组合样本中观察到 MCP-1 的显着连锁（优势比对数 (LOD) = 3.5，78 cM，P = 0.0001），并且在 5 号染色体上的白色样本中观察到暗示性连锁（LOD = 128 cM 时为 1.8，P=0.002）。位于3号染色体连锁峰下方的是趋化因子受体基因簇，包括MCP-1的受体CCR2。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，正如之前针对低密度脂蛋白受体所证明的那样。需要对这些染色体区域进行进一步表征，以确定与 MCP-1 循环水平相关的功能突变。