Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension: Single locus genotype vs. haplotype analysis

Shyh Jong Wu, Fu Tien Chiang, Wei J. Chen, Pi Hua Liu, Kwan Lih Hsu, Juey Jen Hwang, Ling Ping Lai, Jiunn Lee Lin, Chuen Den Tseng, Yung Zu Tseng

Research output: Contribution to journalArticle

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Abstract

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-217A 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 (χ2 = 20.91, P = 0.0008), which was mainly due to the increased frequency of the recombinant haplotypes (-6A ≡ 235M and -6G ≡ 235T), and a pathophysiological role in the predisposition to hypertension was hence indicated. In functional assays, the promoter activities of the haplotypes -217A ≡ -6A and -217G ≡ -6G were significantly higher than the most common haplotype -217G ≡ -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.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalPhysiological Genomics
Volume17
DOIs
Publication statusPublished - Jul 1 2004
Externally publishedYes

Fingerprint

Angiotensinogen
Haplotypes
Single Nucleotide Polymorphism
Genotype
Hypertension
Genes
Linkage Disequilibrium
Homozygote
Genetic Predisposition to Disease
Taiwan

Keywords

  • Genetic polymorphism
  • Linkage disequilibrium
  • Recombination
  • Renin-angiotensin system
  • Transcriptional activity

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension : Single locus genotype vs. haplotype analysis. / Wu, Shyh Jong; Chiang, Fu Tien; Chen, Wei J.; Liu, Pi Hua; Hsu, Kwan Lih; Hwang, Juey Jen; Lai, Ling Ping; Lin, Jiunn Lee; Tseng, Chuen Den; Tseng, Yung Zu.

In: Physiological Genomics, Vol. 17, 01.07.2004, p. 79-86.

Research output: Contribution to journalArticle

Wu, Shyh Jong ; Chiang, Fu Tien ; Chen, Wei J. ; Liu, Pi Hua ; Hsu, Kwan Lih ; Hwang, Juey Jen ; Lai, Ling Ping ; Lin, Jiunn Lee ; Tseng, Chuen Den ; Tseng, Yung Zu. / Three single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension : Single locus genotype vs. haplotype analysis. In: Physiological Genomics. 2004 ; Vol. 17. pp. 79-86.
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T2 - Single locus genotype vs. haplotype analysis

AU - Wu, Shyh Jong

AU - Chiang, Fu Tien

AU - Chen, Wei J.

AU - Liu, Pi Hua

AU - Hsu, Kwan Lih

AU - Hwang, Juey Jen

AU - Lai, Ling Ping

AU - Lin, Jiunn Lee

AU - Tseng, Chuen Den

AU - Tseng, Yung Zu

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AB - 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-217A 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 (χ2 = 20.91, P = 0.0008), which was mainly due to the increased frequency of the recombinant haplotypes (-6A ≡ 235M and -6G ≡ 235T), and a pathophysiological role in the predisposition to hypertension was hence indicated. In functional assays, the promoter activities of the haplotypes -217A ≡ -6A and -217G ≡ -6G were significantly higher than the most common haplotype -217G ≡ -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.

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KW - Renin-angiotensin system

KW - Transcriptional activity

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