250 The polymorphism Trp719Arg in the kinesin-like protein 6 is associated with the presence of late outgrowth endothelial progenitor cells in acute myocardial infarction

详细信息    查看全文

• 作者：Siamak Davani¹ ; Segolene Gambert² ; Francois Schiele³ ; Jean-Pierre Kantelip¹ ; Nicolas Meneveau³
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2011
• 出版时间：January 2011
• 年：2011
• 卷：3
• 期：1
• 页码：82
• 全文大小：50 K

文摘

Background

Much attention is focused on genetic polymorphisms associated with coronary artery disease. A candidate gene controversially associated with risk of coronary events is the kinesin-like protein 6 (KIF6), which is correlated with Trp719Arg polymorphism. In acute myocardial infarction (AMI), endothelial progenitor cells, particularly endothelial colony forming cells (ECFC) are mobilized from bone marrow and correlated with infarct size reduction. We investigated whether there was a relationship between presence of ECFC in AMI at admission and genetic status with regard to the KIF6 Trp719Arg polymorphism (rs20455).

Methods

Forty five patients aged <75 years old referred for a first STEMI or non STEMI AMI. Peripheral blood samples were drawn on admission. Isolated peripheral blood mononuclear cells were obtained by Hypaque-Ficoll density gradient centrifugation and cultured for 4 weeks. Cultured cells were phenotyped to assess the endothelial origin of ECFC. Genomic DNA was extracted in all patients and genotyping for allelic variations of KIF6 was performed.

Results

Subjects were divided into two groups comparing the (Arg/Arg) homozygote variants with patients having a Trp allele. The genotype frequencies were 55 % , 31 % and 13 % for Arg/Arg, Arg/Trp and Trp/Trp respectively. Between groups, higher levels of TnI, CK and CK-MB wer observed in the Arg/Arg group (respectively p = 0.026, p = 0.001 and p = 0.031). ECFC were observed in 33 % of patients with AMI. The percentage of patients without ECFC was significantly higher in the Arg/Arg group (p = 0.033). No other significant differences were observed between groups.

Conclusion

In this report the Arg/Arg group showed a high number of ECFC-negative patients. A possible explanation might be the low mobilization of ECFC from bone marrow in this genotype since KIF6 is involved in cytokinesis. The altered amino acid Trp719Arg could decrease the ECFC released from the bone marrow in response to chemokines released at the onset of AMI.