Association between Gly241Arg ICAM-1 gene polymorphism and serum sICAM-1 concentration in the Stanislas cohort
Association between Gly241Arg ICAM-1 gene polymorphism and serum sICAM-1 concentration in the Stanislas cohort
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DOI：
10.1038/sj.ejhg.5201033
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发表时间：
2003-09-01
影响因子：
5.2
通讯作者：
Visvikis, S
中科院分区：
文献类型：
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作者：
Ponthieux, A;Lambert, D;Visvikis, S
细胞内粘附分子-1 (ICAM-1) 是一种介导活化内皮细胞与白细胞相互作用的细胞粘附分子，参与多种炎症和心血管疾病。然而，这些标记与遗传多态性之间的关系仍有待阐明。本研究的目的是评估 ICAM-1 基因外显子 4 密码子 241 的单碱基多态性对健康人群血清 sICAM-1 浓度的影响，同时考虑 sICAM-1 水平的其他生物决定因素。在从 Stanislas 队列中提取的 413 名 6-21 岁儿童和 363 名 38-55 岁成年人组成的大型健康人群中测量了血清 sICAM-1 水平和 ICAM-1 基因的 G/R241 多态性。 R241 等位基因与较低的 sICAM-1 水平显着相关，并分别解释了儿童和成人 3.4% 和 1.9% 的 sICAM-1 变异。调整协变量后，共显性模式对模型的贡献更大，因为 RR 纯合子效应高于 GR 杂合子效应。此外，还发现 sICAM-1 与吸烟、胰岛素抵抗指数 (HOMA IR)、白细胞介素 6 水平以及碱性磷酸酶和天冬氨酸转氨酶活性之间存在显着的独立关联。总之，本研究揭示了 G/R241 ICAM-1 多态性与血清 sICAM-1 水平之间存在显着相关性，这可能是由于 ICAM-1 与白细胞整合素 Mac-1 蛋白的结合受损所致。
Intracellular adhesion molecule-1 (ICAM-1), a cellular adhesion molecule that mediates the interaction of activated endothelial cells with leukocytes, is involved in various inflammatory and cardiovascular disorders. The relation between these markers and genetic polymorphism, however, remains to be elucidated. The aim of this study is to estimate the effect of a single-base polymorphism at codon 241 in exon 4 of ICAM-1 gene on serum sICAM-1 concentration in a healthy population, taking into account other biological determinants of sICAM-1 level. Serum sICAM-1 levels and the G/R241 polymorphism of the ICAM-1 gene were measured in a large healthy population consisting of 413 children aged 6-21 years and 363 adults aged 38-55 years extracted from the Stanislas cohort. The R241 allele was significantly associated with lower sICAM-1 levels and explained 3.4 and 1.9% of the sICAM-1 variability in children and adults, respectively. A codominant pattern contributed better to the model after adjustment for covariates as the RR homozygote effect was higher than that of the GR heterozygote. Moreover, significant independent associations were found between sICAM-1 and smoking, insulin resistance index (HOMA IR), interleukin-6 level, and alkaline phosphatase and aspartate aminotransferase activities. In conclusion, this study revealed a significant association between the G/R241 ICAM-1 polymorphism and serum sICAM-1 levels, probably due to the impairment in binding of ICAM-1 to leukocyte integrin Mac-1 protein.