https://scholars.lib.ntu.edu.tw/handle/123456789/524271
標題: | A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation | 作者: | SHENG-NAN CHANG CHIA-TI TSAI CHO-KAI WU JEN-KUANG LEE LING-PING LAI Huang S.-W. Huang L.-Y. Tseng C.-D. JIUNN-LEE LIN FU-TIEN CHIANG HWANG, JUEY-JEN |
公開日期: | 2012 | 出版社: | Blackwell Publishing Ltd | 卷: | 272 | 期: | 3 | 起(迄)頁: | 305-315 | 來源出版物: | Journal of Internal Medicine | 摘要: | Objectives. In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. Methods. A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. Results. Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. Conclusion. A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis. ? 2012 The Association for the Publication of the Journal of Internal Medicine. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84865547311&doi=10.1111%2fj.1365-2796.2012.02531.x&partnerID=40&md5=09827809d509cf879eb083d5ccd8798b https://scholars.lib.ntu.edu.tw/handle/123456789/524271 |
ISSN: | 0954-6820 | DOI: | 10.1111/j.1365-2796.2012.02531.x | SDG/關鍵字: | calcium channel L type; procollagen; adult; article; C reactive protein gene; cardiovascular risk; controlled study; exon; female; fibroblast; gene; gene expression; gene function; genetic association; genetic polymorphism; genetic predisposition; genetic variability; genotype; haplotype; heart atrium fibrillation; heart muscle cell; human; major clinical study; male; nucleotide sequence; priority journal; promoter region; regulatory mechanism |
顯示於: | 醫學系 |
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