Genetic risk for atherothrombotic cerebral infarction in individuals stratified by sex or conventional risk factors for atherosclerosis

Abstract

Abstract. The aim of the present study was to assess the genetic risk for atherothrombotic cerebral infarction (ACI) in men and women separately as well as in individuals with or without conventional risk factors for atherosclerosis and thereby to contribute to the personalized prevention of ACI. The study population comprised 2705 unrelated Japanese individuals (1244 men, 1461 women), including 636 subjects (372 men, 264 women) with ACI. Subjects with ACI and controls either had or did not have conventional risk factors for atherosclerosis, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 202 polymorphisms of 152 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that 11 different polymorphisms were significantly (P<0.005) associated with ACI in women or men or in individuals with or without hypertension, hypercholesterolemia, or diabetes mellitus: the 584C➝T polymorphism of LIPG, 5665G➝T of EDN1, and G➝A of CCL11 in women; 677C➝T of MTHFR, 1323C➝T of ITGB2, 3932T➝C of APOE, and -231A➝G of EDNRA in men; -572 G➝C of IL6 in hypertensive individuals; -403G➝A of CCL5 and G➝A of COMT in individuals with hypercholesterolemia; and 3932T➝C of APOE and A➝G of TNFSF4 in diabetic individuals. Polymorphisms associated with ACI may thus differ between women and men as well as among individuals with different risk factors. Stratification of subjects on the basis of sex or conventional risk factors for atherosclerosis may therefore be important in order to achieve the personalized prevention of ACI with the use of genetic information.

Association of endothelial nitric oxide synthase polymorphisms and haplotypes with ischemic stroke in Korean individuals with or without diabetes mellitus

“…Moreover, since abnormalities in the activity of enoS affecting the level of plasma NO have been identified, the enoS gene is a possible candidate gene for susceptibility to stroke (12). Several single nucleotide polymorphisms (SnPs) in this gene have been identified, of which three polymorphisms (-786T>c located in the promoter of the enoS gene, a 27-bp repeat polymorphism in intron 4 and 894G>T in exon 7) have been shown to be associated with iS (13)(14)(15)(16)(17). Most of these studies examined the association of these SnPs with dM or iS individually; little is known regarding the effect of SnPs in the enoS gene on the susceptibility to iS of patients with dM.…”

Nature, nurture and epigenetics

“…The higher levels of Crh and Crhr1 , and downregulation of Esr2 , in the central amygdala transcriptome of females is consistent with the literature (Weiser and Handa, 2009; Weiser et al, 2008). Another gene implicated in human and rodent anxiety disorders is Ptgds (Donner et al, 2008; Hovatta et al, 2005; Le-Niculescu et al, 2011; Yamaguchi et al, 2006), which we found exhibits a two-fold increase in the CA3 of the hippocampus of Stress females, and not in males.…”

Val/Met Polymorphism of the COMT Gene Moderates the Association Between Job Strain and Early Atherosclerosis in Young Men

“…Val allele has been associated with increased risk of myocardial infarction 45 and stroke. 46 On the other hand, some studies have found Met allele to be associated with increased risk of acute coronary events. 47,48 Future studies may shed more light on processes underlying the effects of COMT genotype and the job strain ϫ COMT genotype interaction.…”