Genetic polymorphisms for the study of multifactorial stroke

Abstract

Single-gene disorders explain only a minority of stroke cases. Stroke represents a complex trait, which is usually assumed to be polygenic. On this topic, the role of a wide number of candidate genes has been investigated in stroke through association studies, with controversial results. Therefore, it is difficult for the clinician to establish the validity and the level of clinical applicability of the previously reported associations between genetic factors and stroke. This review is an update and an extensive analysis of the more recent association studies conducted in stroke. We evaluated a number of studies on several candidate genes (including F5, F2, FGA/FGB/FGG, F7, F13A1, vWF, F12, SERPINE1, ITGB3/PLA1/PLA2/ITGA2B, ITGA2, GP1BA, ACE, AGT, NOS3, APOE, LPL, PON1, PDE4D, ALOX5AP, MTHFR, MTR, and CBS), providing a final panel of genes and molecular variants. We categorized this panel in relation to the degree of association with stroke, supported by the results of meta-analyses and case-control studies. Our findings could represent a useful tool to address further molecular investigations and to realize more detailed meta-analyses.

Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans

“…When these puORFs cause physiologically relevant changes in protein levels, as we showed for factor XII, they may cause phenotypic variation. Indeed, the factor XII puORF has been associated with several thromboembolic conditions, although the associations are in contention due to small sample sizes (44). We speculate that other puORFs in our collection (Table S3) may also affect phenotype.…”

Association of Polymorphism Rs699 Angiotensinogen Gene (Agt) With Hemorrhagic and Ischemic Strokes

“…Относительный риск (OR -odds ratio) заболевания по конкретному аллелю или генотипу вычисляли как отношение шансов (ОШ) [12]. Подсчитывали ОШ для оценки ассоциации между определенными генотипами и риском развития заболевания по стандартной формуле OR=a/b × d/c, где a и b -количество больных, имею-щих и не имеющих мутантный генотип, соответственно, По результатам исследования установлено, что частота носителей гомозиготного генотипа по распространенному аллелю (ТТ) у больных инсультом составила 22,4%±3,7, у лиц контрольной группы -32,1%±3,7.…”

“…Ген TNFα расположен на 6-й хромосоме в локусе p21.3, промоторная зона гена TNFα включает 8 полиморфных участ-ков с единичными нуклеотидными заменами, из них наиболее изученными являются C-857T , G-308A и G -237A [12].…”

Phosphodiesterase 4D and 5-lipoxygenase activating protein genes and risk of ischemic stroke in Sardinians

“…11 Extension of the findings to non-Icelandic populations had subsequently led to controversial and conflicting results. 12,13 In the attempt to further elucidate the role of these two genes in the risk of IS, we carried out a case -control association study in a well-characterized, earlier published 14,15 genetically homogenous population from the island of Sardinia, Italy. Based on the earlier reports, we characterized common PDE4D and ALOX5AP gene polymorphisms, for some of which a relevant strength of association with stroke had been described in both Icelandic and other populations.…”