The Siblings With Ischemic Stroke Study (SWISS) Protocol

Background  

Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis.     

Additive effects of <Emphasis Type="Italic">LPL</Emphasis>, <Emphasis Type="Italic">APOA5</Emphasis> and <Emphasis Type="Italic">APOE</Emphasis>variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

Background  

Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information.     

The effect of <Emphasis Type="Italic">ABCA1</Emphasis>gene polymorphisms on ischaemic stroke risk and relationship with lipid profile

Background  

Ischaemic stroke is a common disorder with genetic and environmental components contributing to overall risk. Atherothromboembolic abnormalities, which play a crucial role in the pathogenesis of ischaemic stroke, are often the end result of dysregulation of lipid metabolism. The ATP Binding Cassette Transporter (ABCA1) is a key gene involved in lipid metabolism. It encodes the cholesterol regulatory efflux protein which mediates the transfer of cellular phospholipids and cholesterol to acceptor apolipoproteins such as apolipoprotein A-I (ApoA-I). Common polymorphisms in this gene affect High Density Lipoprotein Cholesterol (HDL-C) and Apolipoprotein A-I levels and so influence the risk of atherosclerosis. This study has assessed the distribution of ABCA1 polymorphisms and haplotype arrangements in patients with ischaemic stroke and compared them to an appropriate control group. It also examined the relationship of these polymorphisms with serum lipid profiles in cases and controls.     

Paraoxonase gene polymorphisms and haplotype analysis in a stroke population

Background  

Paraoxonase (PON) has anti-atherogenic activity due to its protective function against low density lipoprotein (LDL) oxidation. Alteration of enzyme activity due to polymorphisms in the PON genes may influence the development of atheroma and thus affect stroke risk. Three PON genes (PON1, PON2 and PON3) have been identifiedand mapped to chromosome 7.     

No evidence for association between <Emphasis Type="Italic">tau</Emphasis>gene haplotypic variants and susceptibility to Creutzfeldt-Jakob disease

Background  

A polymorphism at codon 129 of the prion protein gene (PRNP) is the only well-known genetic risk factor for Creutzfeldt-Jakob disease (CJD). However, there is increasing evidence that other loci outside the PRNP open reading frame might play a role in CJD aetiology as well.     

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

Background  

Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the CDK4 gene reported to date. Beside those high penetrance genes, certain allelic variants of the MC1R gene modify the risk of developing the disease.     

Analysis of the XRCC1 gene as a modifier of the cerebral response in ischemic stroke

Background  

Although there have been studies of the genetic risk factors in the development of stroke, there have been few investigations of role of genes in the cerebral response to ischemia. The brain responds to ischemia in a series of reactions that ultimately influence the volume of a stroke that, in general, correlates with disability. We hypothesize that polymorphisms in genes encoding proteins involved in these reactions could act as modifiers of this response and impact stroke volume. One of the pathways participating in the cerebral ischemic response involves reactive oxygen species which can cause oxidative damage to nucleic acids. DNA repair mechanisms are in place to protect against such damage and imply a role for DNA repair genes in the response of the brain to ischemia and are potential candidate genes for further investigation.     

Study of the serotonin transporter (<Emphasis Type="Italic">SLC6A4</Emphasis>) and <Emphasis Type="Italic">BDNF</Emphasis> genes in French patients with non syndromic mental deficiency

Background  

Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF) pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (SLC6A4) and the brain-derived neurotrophic factor gene (BDNF), are associated with mental deficiency (MD).     

Polymorphism screening and haplotype analysis of the tryptophan hydroxylase gene (TPH1) and association with bipolar affective disorder in Taiwan

Background  

Disturbances in serotonin neurotransmission are implicated in the etiology of many psychiatric disorders, including bipolar affective disorder (BPD). The tryptophan hydroxylase gene (TPH), which codes for the enzyme catalyzing the rate-limiting step in serotonin biosynthetic pathway, is one of the leading candidate genes for psychiatric and behavioral disorders. In a preliminary study, we found that TPH1 intron7 A218C polymorphism was associated with BPD. This study was designed to investigate sequence variants of the TPH1 gene in Taiwanese and to test whether the TPH1 gene is a susceptibility factor for the BPD.     

<Emphasis Type="Italic">FOXP2</Emphasis> gene and language impairment in schizophrenia: association and epigenetic studies

Background  

Schizophrenia is considered a language related human specific disease. Previous studies have reported evidence of positive selection for schizophrenia-associated genes specific to the human lineage. FOXP2 shows two important features as a convincing candidate gene for schizophrenia vulnerability: FOXP2 is the first gene related to a language disorder, and it has been subject to positive selection in the human lineage.     

Multiple interactions between the alpha<Subscript>2C</Subscript>- and beta<Subscript>1</Subscript>-adrenergic receptors influence heart failure survival

Background  

Persistent stimulation of cardiac β₁-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α_2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively) on the risk of death/transplant in heart failure patients.     

Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene <Emphasis Type="Italic">KCNN3</Emphasis> and migraine susceptibility

Background  

Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels.     

The association of CTLA‐4 and CD28 gene polymorphisms with idiopathic ischemic stroke in the paediatric population

Autoimmune vasculitis is believed to be a critical factor in the development of idiopathic childhood ischemic stroke. The association of polymorphisms in CTLA‐4 and CD28 with some immune vasculitides, such as systemic lupus erythematosus (SLE) and Behçet's disease has been reported. The aim of the present study is to investigate the association of the genetic variants in the CTLA‐4 and CD28 genes of children who suffered idiopathic ischemic stroke using a case–control design. Two single nucleotide polymorphisms (SNPs) in the CTLA‐4 gene and an SNP in the CD28 gene were genotyped in 51 patients who suffered idiopathic ischemic stroke, and in 74 healthy controls from mainland China. An SNP, CTLA‐4+49A/G located in exon 1 of the CTLA‐4 gene, showed nominal association with the disease (P = 0.012, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.17–3.73) using allele‐based analysis. Homozygous carriers of the G allele of this SNP were more common in the patients than in the controls (P = 0.008). The CD28IVS3 +17TT genotype was found to be more common in the patients than in the controls (P = 0.039, OR = 2.96, 95% CI = 1.02–8.58). No correlations of at‐risk genotype (G/G) of CTLA‐4+49A/G and genotype (T/T) of CD28+17T/C with the main clinical features of idiopathic childhood ischemic stroke were observed. The results suggest that polymorphisms in the CTLA‐4 and CD28 genes may contribute to the increased risk of idiopathic ischemic stroke.     

No germline mutations in supposed tumour suppressor genes <Emphasis Type="Italic">SAFB1</Emphasis> and <Emphasis Type="Italic">SAFB2</Emphasis>in familial breast cancer with linkage to 19p

Background  

The scaffold attachment factor B1 and B2 genes, SAFB1/SAFB2 (both located on chromosome 19p13.3) have recently been suggested as tumour suppressor genes involved in breast cancer development. The assumption was based on functional properties of the two genes and loss of heterozygosity of intragenic markers in breast tumours further strengthened the postulated hypothesis. In addition, linkage studies in Swedish breast cancer families also indicate the presence of a susceptibility gene for breast cancer at the 19p locus. Somatic mutations in SAFB1/SAFB2 have been detected in breast tumours, but to our knowledge no studies on germline mutations have been reported. In this study we investigated the possible involvement of SAFB1/SAFB2 on familiar breast cancer by inherited mutations in either of the two genes.     

Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families: the Family Study of Stroke Risk and Carotid Atherosclerosis

Background  

Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families.     

Two-stage case-control association study of dopamine-related genes and migraine

Background  

We previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism: MAOA in migraine without aura and DDC in migraine with aura. Herein we investigate the contribution to migraine susceptibility of eight additional genes involved in dopamine neurotransmission.     

Polymorphisms of the Flavin containing monooxygenase 3 (<Emphasis Type="Italic">FMO3</Emphasis>) gene do not predispose to essential hypertension in Caucasians

Background  

The recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension.     

Genetic variation of NEDD4L is associated with essential hypertension in female Kazakh general population: a case-control study

Background  

Hypertension affects > 18.8% of adults in China. Indeed, hypertension is the most prevalent risk factor for cardiovascular morbidity and mortality worldwide. Genetic variation is thought to contribute to the etiology of hypertension. NEDD4L is a candidate gene for hypertension, both functionally and genetically. The purpose of the current study was to investigate the relationship between the variation in NEDD4L and essential hypertension in Kazakh, which is a relatively isolated population with a pure genetic background and is an ideal population to study genetic mechanisms of hypertension.