gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

A novel G alpha q promoter SNP increases transcriptional activity and the risk for cardiac hypertrophy

neuartiger G alpha q Promotor Polymorphismus erhöht die transkriptionelle Aktivität und das Risiko für kardiale Hypertrophie

Meeting Abstract (Hypertonie 2004)

  • U.H. Frey - GSF Forschungszentrum (Neuherberg, D)
  • D. Savidou - GSF Forschungszentrum (Neuherberg, D)
  • W. Lieb - Innere Medizin II (Lübeck, D)
  • J. Erdmann - Innere Medizin II (Lübeck, D)
  • A. Döring - Innere Medizin II (Lübeck, D)
  • H. Schunkert - Innere Medizin II (Lübeck, D)
  • W. Siffert - Uniklinikum Essen (Essen, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP61

The electronic version of this article is the complete one and can be found online at:

Published: August 10, 2005

© 2005 Frey et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Cardiac overexpression of Galphaq results in left ventricular hypertrophy (LVH), apoptosis, and heart failure while the underlying mechanism is unknown. We, therefore, cloned the 5´-flanking region of the human GNAQ gene encoding Galphaq and characterized its promoter activity through reporter assays and electrophoretic mobility shift assays (EMSA) in HEK293 cells. A subsample of participants from the population-based MONICA Augsburg Survey 1994/95 (n=1139; without lipid-lowering medications; age 25-74 years) which were studied by questionnaire, physical examination, and biochemical analyses were genotyped to associate genotypes with echocardiographic data of LVH. Using human heart cDNA, multiple transcription initiation sites were identified, the most 5´ one matching precisely the consensus sequence for a transcription initiator element. We then identified the promoter region controlling basal transcription followed by sequencing of the whole promoter which revealed a common (frequency: 47.3%) SNP at position -694/-695 resulting in an exchange of two nucleotides (GC>TT). EMSA experiments demonstrated an increased binding of the transcription factor SP-1 to GC genotype constructs. Promoter constructs with the GC genotype showed two-fold significantly increased promoter activity following stimulation with 10% serum or 10 nM angiotensin II. Individuals from the MONICA survey with the GC genotype revealed a higher risk for developing LVH compared to TTs (OR: 3.28; p = 0.016), this effect being most pronounced in women (OR: 6.1; p = 0.021). Accordingly, the left ventricular mass index was higher in GCs compared to TTs, again, this effect being most prominent in women (adjusted means for known confounders: 81.2 vs. 76.8; p = 0.019). We conclude, that a novel polymorphism in the Galphaq promoter region affects binding of SP-1 and is associated with enhanced promoter activity and increased risk for LVH.