Artikel
Angiotensiogen (AGT) Promoter Haplotyes are Associated With Bloot Pressure in Untreated Hypertensives
Assoziation von Angiotensinogen (AGT)-Promoter-Haplotypen mit Blutdruck bei unbehandelten Hypertonikern
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Veröffentlicht: | 10. August 2005 |
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Objectives: The polymorphic angiotensinogen (AGT) gene is one of the most promising candidate genes for blood pressure (BP) phenotypes and essential hypertension and some reports point to a superiority of haplotype compared to single polymorphism analysis.
Methods: We genotyped a Caucasian study population comprising hypertensive subjects (n = 704) with and without antihypertensive medication for the AGT polymorphisms C-532T, A-20C, C-18T, and G-6A and investigated whether AGT promoter haplotypes rather than AGT single variants separately were associated with various BP phenotypes available in our study population.
Results: In single variant analyses, hypertensive patients without medication, carrying the AGT -532T or -6A alleles had significantly higher SBP, DBP, as well as ambulatory BP values compared to respective non-carriers. In haplotype-based analyses, combining all four AGT promoter variants, we demonstrate that AGT haplotypes containing different allele combinations at positions -532 and -6 were significantly associated with different BP values: (1) -532T and -6A with higher, (2) -532C and -6G with lower, (3) -532C and -6A with intermediate BP values. Since the result for the -532C/-20A/-18C/-6G haplotype was due to differences between non-carriers and carriers of this haplotype on both chromosomes, a recessive inheritance model for BP effects could be assumed.
Conclusions: Our results designate the C-532T and G-6A as the best candidates for functional studies on the AGT gene. Haplotype-based analyses should greatly aid in the dissection of the genetic basis of complex traits, such as BP and hypertension.