Cardiovascular diseases and G-protein β3 subunit gene (GNB3) in the era of genomewide scans

Abstract

The last 4 years were the era of genomewide scans in cardiovascular genetics. Since 1999, after publication of the first comprehensive genome linkage analysis of systolic blood pressure in humans, 1 more than 20 genomewide searches for hypertension genes have been reported. The number of detected cardiovascular quantitative trait loci (QTLs) has increased rapidly, forming a new dense QTL-map within the human genome. At present, a QTL for blood pressure or hypertension exists almost on every human chromosome. However, most of the detected QTLs do not overlap, even within populations of the same ethnic origin. Much remains to be done in further dissection of these regions in order to identify new, consistent positional genetic candidates of human hypertension. The use of such identified positional markers is needed in association studies following genomewide searches and remains a promising strategy in cardiovascular genetics. However, most of the genes tested currently for association with essential hypertension and related phenotypes are not identified based on their positional relation to a detected QTL but on their pathophysiological potential to affect cardiovascular functions. Approximately 100 genes have been tested as candidates in association studies with cardiovascular traits including left ventricular hypertrophy (LVH) and essential hypertension.The expression of genes encoding components of the renin-angiotensin system is upregulated in vascular and cardiac hypertrophy and remodelling.The ability of angiotensin-converting enzyme (ACE) inhibitors to induce the regression of hypertensive LVH and prevent ventricular remodelling after myocardial infarction provides a clinical correlate to these observations. Thus, insertion/deletion (I/D) polymorphism of the ACE gene has been tested as a potential risk factor of hypertensive LVH in numerous studies, and the proportion of negative and positive results appears to be roughly equal. 2 Studies on association between hypertensive LVH and polymorphisms within the genes encoding angiotensinogen and angiotensin II receptors have also provided conflicting results. 2 Single nucleotide polymorphisms (SNPs) within genes encoding G-protein subunits belong to the most promising candidates in investigations on genetic determinants of LVH and essential hypertension, since the most important receptors in cardiovascular system have been linked to these intracellular signal messengers. 3 A SNP in exon 10 (C825T) of the G-protein b3 subunit gene is associated with alternative splicing. 4 The splice variant (Gb3s) occurring with T allele has been shown to enhance intracellular signal transmission with a potential to affect vascular reactivity, and cell growth. 5 These functional consequences of C825T polymorphism demonstrated at a molecular level as well as ubiquitous expression of this gene in cardiovascular system make the GNB3 an optimal target in pursuit of genes for human hypertension and its cardiac complications. In addition, the early studies in Caucasian populations ha...

Fibroblast Growth Factor 1 Gene and Hypertension

“…2 The polygenic nature of essential hypertension is well documented by genomewide scans that identified several independent quantitative trait loci (QTLs) for blood pressure (BP). 2 Although BP QTLs are present on almost every human chromosome, 3 only a few genomic regions were linked to BP in Ͼ1 investigation. One of these unique chromosomal segments is the distal portion of the long arm of chromosome 5 (5q23.1 to 5q35.2).…”

Συσχέτιση Του Πολυμορφισμού A1166C Του Υποδοχέα Τύπου 1 Της Αγγειοτενσίνης ΙΙ Με Δείκτες Φλεγμονής Σε Ασθενείς Με Αρτηριακή Υπέρταση

“…Σε ότι αφορά το γονιδιακό της τοπίο, θεωρείται σύνθετη ετερογενής και πολυγονιδιακή νόσος, σύμφωνα με στοιχεία από πολυάριθμες μελέτες για αρκετές χρωμοσωμικές περιοχές που φαίνεται να συνδέονται με την ΑΥ. Αυτά τα γενωμικά (genomic) τμήματα είναι γνωστά ως BT-QTLs και είναι παρόντα σε όλα σχεδόν τα ανθρώπινα χρωμοσώματα (13,14). (181,184).…”