Linked Life Data

11927836

Source:http://linkedlifedata.com/resource/pubmed/id/11927836

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-4-2
pubmed:abstractText
The 825T-allele of the gene GNB3 encoding the G protein beta3 subunit is associated with hypertension and obesity, and identifies individuals highly responsive to diuretic therapy. Gbeta3s, a Gbeta3 protein variant generated by alternative splicing in carriers of the 825T-allele, is linked to increased signal transduction and is a potential cause for the observed pathophysiology. Here, we searched the entire GNB3 gene for additional polymorphisms and analysed their prevalence in Caucasian, black African and Asian populations. We detected six novel single nucleotide polymorphisms which were termed according to their location as G76A, G1906T, G2906A, A3882C, G5177A, and G5249A. Furthermore, we found a CACA-insertion-deletion polymorphism at position 6496. Genotyping and association studies resulted in the definition of two major GNB3 haplotypes, termed 'C-haplotype' (alleles 825C, 3882A, 5249G, 6496CACA-) and 'T-haplotype' (alleles 825T, 3882C, 5249A, 6496CACA+). Molecular modelling studies revealed that the pre-mRNA structures of both haplotypes exhibit marked differences which may account for the alternative splicing predominantly observed with the T-haplotype. The prevalence of these haplotypes in major ethnic populations differs considerably. Furthermore, we detected additional frequent GNB3 polymorphisms. These variants were restricted to one or two major ethnic populations. Our results will aid future studies on population-specific effects of the GNB3 variants on risk and course of frequent diseases, including hypertension, obesity, stroke and myocardial infarction. Furthermore, they will contribute to the understanding of GNB3-related population-specific pharmacogenetic differences in the response to major drugs, as already shown for diuretics and antidepressants.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-20
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Identification and ethnic distribution of major haplotypes in the gene GNB3 encoding the G-protein beta3 subunit.
pubmed:affiliation
Institut für Pharmakologie, Universitätsklinikum Essen, Essen, Germany. dieter.rosskopf@uni-essen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't