https://scholars.lib.ntu.edu.tw/handle/123456789/202204
標題: | Three Single-Nucleotide Polymorphisms of the Angiotensinogen Gene and Susceptibility to Hypertension: Single Locus Genotype Vs. Haplotype Analysis | 作者: | WU, SHYH-JONG FU-TIEN CHIANG WEI J. CHEN LIU, PI-HUA HSU, KWAN-LIH JUEY-JEN HWANG LING-PING LAI JIUNN-LEE LIN TSENG, CHUEN-DEN TSENG, YUNG-ZU |
關鍵字: | renin-angiotensin system;genetic polymorphism;linkage disequilibrium;recombination;transcriptional activity | 公開日期: | 七月-2004 | 卷: | 17 | 期: | 2 | 起(迄)頁: | 79 | 來源出版物: | PHYSIOLOGICAL GENOMICS | 摘要: | Although some single polymorphism analyses of the angiotensinogen (AGT) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single- nucleotide polymorphisms (SNPs) (G-217A, A-6G, and M235T) in the AGT gene with hypertension. In a sample of 461 hypertensive and 327 normotensive patients in Taiwan, we found that -217AA and -6GG homozygotes conferred independently an increased risk to hypertension (P = 0.008 and P = 0.037, respectively), as illustrated by their significant associations with hypertension in both single SNP and pair-wise SNPs analyses. Meanwhile, a very weak linkage disequilibrium was found between the G -17A and the A-6G polymorphisms in terms of r(2) (< 0.05). On the basis of likelihood ratio test, only the set of haplotypes that constituted the A-6G and the M235T polymorphisms was associated with hypertension (χ(2) = 20.91, P = 0.0008) , which was mainly due to the increased frequency of the recombinant haplotypes (-6A &EQUIV; 235M and -6G &EQUIV; 235 T), and a pathophysiological role in the predisposition to hypertension was hence indicated. In functional assays, the promoter activities of the haplotypes -217A &EQUIV; -6A and- 217G &EQUIV; -6G were significantly higher than the most common haplotype -217G &EQUIV; -6A. These results highlight the necessity of a thorough analysis of all reported variants of a candidate gene in the elucidation of genetic susceptibility to a complex disease like hypertension, even when the variants are in the same haplotype block. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/103407 https://www.scopus.com/record/display.uri?eid=2-s2.0-3843067473&doi=10.1152%2fphysiolgenomics.00133.2003&origin=inward&txGid=dea5edc710b5559816dfee12714b1339 |
DOI: | 10.1152/physiolgenomics.00133.2003 |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。