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The progress of research into interleukin gene polymorphism associated with stroke  [cached]
Chen CHEN,Xiao-Yuan QIAO,Guang-xi SHANG,Jin-Tao WANG
Medical Journal of Chinese People's Liberation Army , 2013,
Abstract: As a common disease, stroke seriously impairs human health. Interleukin (IL) is an important type of inflammatory mediators, which is involved in the pathogenesis of stroke. With the study of genomics, we discovered that some gene loci of IL were associated with stroke, such as IL-1α-889 C/T, IL-1RN rs380092 and IL-10-1082 G/G. Meanwhile, some gene loci of IL might become independent risk factors of stroke, such as IL-4 C582T and IL4-589C>T. Therefore, the IL gene polymorphism had become a research focus in pathogenesis of stroke. Our paper describes the relationship between IL subtype and its gene polymorphism with stroke. We look forward to provide a useful information for further research.
Association of interleukin-1 gene cluster polymorphisms with ischemic stroke in a Chinese population  [cached]
Lai Jiangtao,Zhou Dongchen,Xia Shudong,Shang Yunpeng
Neurology India , 2006,
Abstract: Background and Aims: Chronic inflammatory process plays an important role in atherothrombosis. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response and its activity is critically regulated by its receptor antagonist (IL-1Ra). A variable number tandem repeat polymorphism in intron 2 of IL-1Ra gene and a C to T single base polymorphism in the promoter of IL-1β gene (C-511 T) have been reported to affect the levels of IL-1 as well as its antagonist, IL-1Ra. It is also reported in several studies that these polymorphisms are associated with the susceptibility to cardio-cerebral vascular disease. However, data are limited in China. In this article, we studied the relationships between these polymorphisms and the risk of ischemic stroke in China. Materials and Methods: One hundred and twelve patients committed ischemic stroke were compared with 95 demographically matched healthy volunteers. Results: The frequencies of the IL-1Ra 1/1 genotype and IL-1Ra allele 1 (RaFNx011 allele) in stroke patients were significantly higher than those in healthy volunteers [93.7% vs. 82.1%, P =0.014; 0.964 vs. 0.905, P =0.007]. No significant differences were found in the IL-1β -511 genotype and the allele distribution between the two groups. Conclusions: Our results implicated that IL-1 gene polymorphism might be associated with the susceptibility to ischemic stroke.
Role of MTHFR C677T polymorphism in ischemic stroke  [cached]
Panigrahi Inusha,Chatterjee Tathagata,Biswas Arijit,Behari Madhuri
Neurology India , 2006,
Abstract: Background: Homozygosity for MTHFR C677T polymorphism can lead to significantly high homocysteine levels and hyperhomocysteinemia is an important risk factor for thrombotic events. Aims: The aim was to determine role of MTHFR C677T polymorphism in North Indians with ischemic stroke. Settings and Design: In a prospective study, the subjects of stroke were recruited from the neurology clinic of the hospital. Controls were healthy individuals from the Hematology clinic without any history of stroke. Materials and Methods: Plasma homocysteine levels were measured by enzyme immuno assay method after 3 months of acute episode. Serum folate and Vitamin B12 levels were estimated by competitive inhibition radioassay. MTHFR polymorphism was detected by PCR-RFLP using Hinf I enzyme. Statistical analysis: The analysis of significance of results was done using SPSS software package. A pvalue < 0.05 was taken as significant. Results: Thirty-two acute ischemic stroke patients (aged 1-44 years) were studied. Fourteen (43.8%) had recurrent stroke. Nine (28%) had multiple infarcts. Four of 32 patients (12.5%) had high homocysteine levels. Three out of these 4 hyper-homocysteinemia patients were homozygous ( TT ) for MTHFR polymorphism (2 with recurrent stroke). Two of three homozygous cases with TT genotype had low serum folate. Five of 32 stroke cases (18.8%) were heterozygous ( CT ) genotype. Conclusions: Primary hyper-homocysteinemia appears to be an important risk factor for ischemic stroke in North Indians, most due to MTHFR C677T homozygosity. Folate levels may modify the presentation of the MTHFR TT genotype.
Low Ankle Brachial Index in Acute Ischemic Stroke: Does ApoE Gene Polymorphism Have a Role?  [PDF]
Shaimaa El-Jaafary, Mohamed El-Tamawy, Hassan Hosny, Mona Fathy, Foad Abd-Allah, Ehab Shaker
World Journal of Cardiovascular Diseases (WJCD) , 2015, DOI: 10.4236/wjcd.2015.52006
Abstract: Background: The existence of asymptomatic peripheral arterial disease among patients with acute ischemic stroke has been studied and proved. Low ankle brachial index (ABI) is considered as a marker of atherosclerosis, and its relation to stroke severity was documented in some studies. The effect of different alleles of ApoE gene on acute ischemic stroke presentation in patients with low ABI is not known. Objective: To study the effect of ApoE gene polymorphism on stroke severity, outcome and recurrence in patients with asymptomatic peripheral arterial disease identified by low ABI. Methods: Patients with acute ischemic stroke were screened for the presence of asymp-tomatic peripheral arterial disease by estimating the ABI using a pocket Doppler ultrasound device. Assay of ApoE gene was done using the real-time PCR technique. Results: Low ABI was present in 31% of patients with acute ischemic stroke. There was no significant difference among patients with different ApoE alleles regarding the severity of their symptoms. Also, there was no significant difference among patients with normal ABI and those with abnormal ABI regarding the ApoE gene polymorphism. Conclusion: The current study showed that there was no significant relation between ApoE gene polymorphism and low ABI in ischemic stroke patients who had asymptomatic peripheral arterial disease.
Polymorphism of the methylenetetrahydrofolate reductase gene association with homocysteine and ischemic stroke in type 2 diabetes
Sun Jia-Zhong,Xu Yancheng,Lu Hongyun,Zhu Yilian
Neurology India , 2009,
Abstract: Background : Ischemic stroke is a frequent heterogeneous multifactorial disease. A number of genetic mutations and environmental factors have been implicated. A polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with hyperhomocysteinemia a risk for atherosclerotic vascular diseases. Aim : A cross-sectional study was performed to determine the relationship between the gene polymorphism for MTHFR and ischemic stroke in type 2 diabetes mellitus. Materials and Methods : Of the 215 unrelated patients with type 2 diabetes mellitus recruited, 119 patients had ischemic stroke, Control group included 142 healthy subjects. The genotype of the subjects for the C677T polymorphism of MTHFR was analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by HinfI digestion. Plasma total homocysteine (Hcy) levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. Results : The genotype distribution did not differ between the control subjects and type 2 diabetic patients (P > 0.05). Plasma homocysteine levels were markedly higher in diabetic patients with TT genotype than those with CC or CT genotype (P > 0.05). Ischemic stroke was more frequently observed in type 2 diabetic patients with the TT genotype than in those with the CT and CC genotype (odds ratio=4.04, 95% CI=1.95-8.34, P=0.0036). Logistic regression analysis revealed that the C677T mutation of MTHFR gene was independently associated with ischemic stroke in type 2 diabetes. Conclusion : MTHFR C677T gene polymorphism associated with a predisposition to hyperhomocysteinemia could constitute a useful predictive marker for ischemic stroke in type 2 diabetic Chinese patients.
Relationship of Serum Interleukin-10 and Its Genetic Variations with Ischemic Stroke in a Chinese General Population  [PDF]
Gaoqiang Xie, Phyo Kyaw Myint, M. Justin S. Zaman, Ying Li, Liancheng Zhao, Ping Shi, Fuxiu Ren, Yangfeng Wu
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074126
Abstract: Background and Purpose Anti-inflammatory cytokine and its genetic variations may play an important role in the process of atherosclerosis. We assessed whether serum interleukin-10 (IL-10) and its genetic variations are associated with ischemic stroke in a Chinese general population. Methods An epidemiological survey on cardiovascular diseases and their risk factors was carried in a general population in Beijing in 2005. Serum IL-10, IL-6, p-selectin, soluble intercellular adhesion molecule-1 and C-reactive protein were analyzed using ELISA kits, while three IL-10 Single Nucleotide Polymorphisms (SNP) (rs1800872, rs1554286 and rs3021094) were genotyped in 1475 participants. Results A high serum IL-10 (top tertile) was significantly associated with ischemic stroke (multivariable adjusted odds ratio (OR) =0.50; 95%CI 0.31-0.81). Rs1800872 (AA vs. AC+CC genotype, OR=1.60; 1.06-2.39), rs1554286(TT vs. CT+CC genotype, OR=1.59; 1.06-2.39), and rs3021094 (CC/CA vs. AA genotype, OR=1.64; 1.04-2.60) were all significantly associated with ischemic stroke even after controlling for age, sex, smoking, systolic blood pressure, total cholesterol, glucose, body mass index and serum IL-10. The SNP score (a summary index of these SNPs) and IL-10 (top tertile) together significantly improved the discriminative power in predicting ischemic stroke by 3.3% (95%CI: 0.2-6.4, p=0.0398) compared to predictions based on conventional risk factors alone. Conclusions The lower serum IL-10 concentration and its selected genetic variations were significantly associated with an increased likelihood of ischemic stroke in this cross-sectional study. Our results suggest that more prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 and its SNPs as new biomarkers to identify a predisposition towards ischemic stroke.
Methylenetetrahydrofolate reductase C677T polymorphism in Iraqi patients with ischemic stroke  [cached]
Al-Allawi Nasir,Avo Arteen,Jubrael Jaladet
Neurology India , 2009,
Abstract: Background: Data are conflicting concerning the association between ischemic stroke and methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Studies addressing this matter in developing countries are limited. Aim: This study was undertaken to evaluate MTHFR C677T gene polymorphism as a possible risk factor in patients with ischemic stroke in Iraq. Settings and Design: A case-control study in a major teaching hospital in Northern Iraq. Materials and Methods: Study population included 70 patients with ischemic stroke diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI) and 50 controls matched by age and sex. All the patients and controls had detailed neurologic examination and blood sugar, lipid profile, total homocysteine, as well as, MTHFR gene analysis. The MTHFR C677T mutation status was detected in the amplified products using reverse hybridization to specific mutant and wild oligonucleotide probes by a colorimetric microwell plate method. Statistical Analysis: Mann-Whitney U test and Chi-square tests were used to find the significance. Results: The median age of the patients was 60 years and 54% were males. The MTHFR C677T gene analysis detected TT genotype in 20% of patients and in 6% of controls and CC genotype in 37% of the patients and in 54% of the controls. The calculated risk of ischemic stroke in the subjects with TT genotype was 4.85 times more than the subjects with CC genotype (P=0.03). Serum homocysteine level was significantly higher in the patients than the controls (P=0.02). The serum homocysteine levels were significantly higher in those with TT and CT genotypes when compared to those with CC genotype (P < 0.001 and P=0.04, respectively). Conclusion: In the Iraq population studied MTHFR C677T TT genotype was a significant risk factor for ischemic stroke and it was related to the increased total homocysteine levels and the risk for ischemic stroke was graded with increasing MTHFR 677T allele dose.
Role of Interleukin-6 Correlated to C. pneumoniae Infection as a Biomarker for Prediction of Stroke Severity in Young Patients with Acute Ischemic Stroke  [PDF]
M. V. Padma Srivastava,Ashu Bhasin,Rama Chaudhry,Sakshi Sharma,S. Vivekanandhan,Rohit Bhatia,Manjari Tripathi
Asian Journal of Neuroscience , 2014, DOI: 10.1155/2014/649106
Abstract: Background. Stroke in young is the leading cause of morbidity and mortality in the Indian subcontinent with a reported incidence of 15–30% of all stroke patients. The mechanisms for stroke in the young may include unconventional risk factors such as infections. Causative role of C. pneumoniae infection in patients with acute ischemic stroke (AIS) remains unresolved till date, although the link between C. pneumoniae and cerebrovascular disease has been investigated in many studies. This study examined the upregulation of IL-6 after acute cerebral ischemia and correlated the same with the C. pneumoniae antibody titres (IgG, IgA, and IgM). Methods. We studied blood samples from eighty ( ) acute stroke patients and healthy age- and sex-matched controls. Venous blood samples were drawn within one week from the onset of stroke. Detection of IgA, IgG, and IgM antibodies to C. pneumoniae was done with a validated microimmunofluorescence (MIF) technique from 5?mL of serum in all subjects. Interleukin-6 was estimated with sandwich ELISA method. Results. The IL-6 levels were elevated in patients with a mean 28.9 ± 8.6?pg/mL as compared to 4.7 + 1.8?pg/mL in healthy age-matched controls (95% CI: 37.7 to 78.4; ). On correlation of IL-6 to stroke severity, it was found that 30 patients with NIHSS between 0 and 15 had mean IL-6 of 24.6?pg/mL and 50 patients had NIHSS of 18.8 (severely affected) with a mean IL-6 of 43.8?pg/mL. On multivariate analysis after adjusting for sex, hypertension, diabetes mellitus, smoking, and alcohol, the IgA seropositivity yielded an adjusted OR for stroke (4.72; 95% CI: 1.61, 13.83; ), while IgG seropositivity did not show a statistically significant result. We also observed that 81% of cases were seropositive for IgA versus 32% of controls ( ) followed by IgG, as 52.7% of cases were seropositive versus 17.3% of controls ( ). Multiple regression analysis was done with IL-6 as dependent variable to antibody with IL-6 as dependent variable to Cp-IgA, Cp-IgG, and IgM with 10.4% change in the IL-6 titres showing statistical significant result = 3.32, . Conclusions. IL-6 has important role after acute ischemic stroke and is correlated with stroke severity and may correlate to acute or chronic infectious states with C. pneumonia. 1. Introduction Young stroke patients constitute 15–30% of all stroke patients in India, to that of 3.0–8.5% of all stroke patients reported from the West [1]. Stroke in young, including stroke in children and young adults (<45 years), is an important cause of morbidity throughout the world, especially in developing
Association of Functional VKORC1 Promoter Polymorphism with Occurrence and Clinical Aspects of Ischemic Stroke in a Greek Population  [PDF]
Georgia Ragia,Stella Marousi,John Ellul,Vangelis G. Manolopoulos,Anna Tavridou
Disease Markers , 2013, DOI: 10.1155/2013/769574
Abstract: Genetic factors are considered to play an important role in determining the susceptibility to the occurrence, clinical course, and functional outcome of an acute ischemic stroke (IS). Undercarboxylation of specific vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can affect both vascular calcification and thrombogenicity. We sought to determine the association of VKORC1 ?1639G > A polymorphism with IS incidence, age of onset, severity of disease, and functional outcome after an acute IS. VKORC1 ?1639G > A polymorphism was determined in 145 consecutive patients with first ever IS and 145 age- and sex-matched control subjects of Greek Caucasian origin using PCR-RFLP. Stroke severity and functional outcome were assessed on admission and at one month after stroke, respectively. Frequency of VKORC1 ?1639G > A genotypes did not differ between IS patients and controls ( , ). Moreover, carriage of the A allele was not associated with age of stroke onset, severity of disease (Scandinavian stroke scale score 32.2 versus 32.9, resp., ), or poor outcome at 1 month post-stroke (52.9 versus 64.4%, resp., ). In conclusion, VKORC1 ?1639G > A polymorphism is not a genetic determinant of IS occurrence, age of onset, severity, or functional outcome of disease in a Greek population. 1. Introduction Ischemic stroke (IS), a multifactorial disease which shares many common risk factors with coronary artery disease, leads to a high mortality and disability rate [1]. However, distinct mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events. Both environmental and genetic factors are considered to play important role in determining the susceptibility to the occurrence, clinical course, and functional outcome of an acute IS. There is evidence that common variants in several genes, each exerting a modest effect, contribute to the risk of stroke [2]. Vitamin K-dependent proteins play a significant role in coagulation but also in bone metabolism and vascular calcification. Modification by -carboxylation is necessary for vitamin K-dependent proteins to become biologically active [3]. Vitamin K epoxide reductase complex subunit 1 (VKORC1) is involved in this process by mediating recycling of vitamin K 2,3 epoxide to vitamin K hydroquinone [4], a cofactor for the conversion of glutamate to -carboxyglutamic acid. VKORC1 is the target of coumarin derivatives, and several genetic variations of the VKORC1 gene influence response to anticoagulant therapy (for review, see [5]). Matrix Gla protein (MGP), a vitamin K-dependent
Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes to Ischemic Stroke Risk: A Meta-Analysis of 50 Case-Control Studies  [PDF]
Zhizhong Zhang, Gelin Xu, Dezhi Liu, Xinying Fan, Wusheng Zhu, Xinfeng Liu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046495
Abstract: Background Many studies have investigated the association between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of ischemic stroke. However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous populations. To shed light on these inconclusive findings, we conducted a large meta-analysis of studies relating the ACE I/D polymorphism to the risk of ischemic stroke. Methods Relevant studies were identified by searching PubMed and Embase through February 2012 and by reviewing the references of retrieved articles. We included studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between this polymorphism and ischemic stroke risk. Results Fifty independent publications, with 10 070 stroke cases and 22 103 controls, were included. The results indicated that the DD homozygote carriers had a 37% higher risk of ischemic stroke when compared with the homozygotes II and heterozygote ID [odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.22–1.53]. Subgroup analyses indicated that this higher risk was more pronounced among Asians, hospital-based studies, and small vessel disease (SVD). Potential publication bias may exist, but correction for this bias using a formal statistical method did not materially alter the combined risk estimate. Conclusion The results of our meta-analysis indicate that the D allele of ACE I/D polymorphism is a low-penetrance susceptibility marker of ischemic stroke.
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