Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Identification and ethnic distribution of major haplotypes in the gene GNB3 encoding the G-protein beta3 subunit. 1192 36

The product of the growth arrest-specific gene 6 (GAS6), a ligand for tyrosine kinase receptors, is a vitamin K-dependent protein, structurally related to anticoagulant protein S. Gas6-deficient mice are protected against thrombosis, demonstrating the importance of this protein in the cardiovascular system. In a preliminary study on GAS6 polymorphisms and atherothrombotic disease we found an association between the AA genotype of the c.834 + 7G > A GAS6 polymorphism and stroke. In order to further explore this association by considering GAS6 haplotypes and the main stroke subtypes, 457 patients with ischemic stroke, 199 with hemorrhagic stroke and 150 asymptomatic controls were genotyped for eight GAS6 polymorphisms and other genetic markers in the same genome region. Association was measured by logistic regression analysis. The THESIAS program was used to measure linkage disequilibrium and haplotype frequencies. In univariate analysis, the GAS6 c.834 + 7AA genotype was found associated with decreased risk for stroke (OR: 0.59; 95%CI: 0.37-0.93). After adjustment for vascular risk factors, association was maintained when stroke subtypes affecting the microvasculature such as lacunar stroke and deep haemorrhage, were grouped together (OR: 0.44; 95%CI: 0.21-0.90). Furthermore, haplotype analysis revealed that association was even stronger when the c.834 + 7A allele was present in a specific haplotype (CACA) of four GAS6 polymorphisms. From these results we conclude that the A allele of the GAS6 c.834 + 7G > A polymorphism and more specifically, the CACA haplotype, is less prevalent in patients with stroke, suggesting a protective role for stroke of this haplotype.
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PMID:Association of specific haplotypes of GAS6 gene with stroke. 1772 24