A replication study of genetic risk loci for ischemic stroke in a Dutch population: a case-control study.
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ABSTRACT:
SUBMITTER: Hauer AJ
PROVIDER: S-EPMC5610184 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
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A replication study of genetic risk loci for ischemic stroke in a Dutch population: a case-control study.
Hauer Allard J AJ Pulit Sara L SL van den Berg Leonard H LH de Bakker Paul I W PIW Veldink Jan H JH Ruigrok Ynte M YM
Scientific reports 20170922 1
We aimed to replicate reported associations of 10 SNPs at eight distinct loci with overall ischemic stroke (IS) and its subtypes in an independent cohort of Dutch IS patients. We included 1,375 IS patients enrolled in a prospective multicenter hospital-based cohort in the Netherlands, and 1,533 population-level controls of Dutch descent. We tested these SNPs for association with overall IS and its subtypes (large artery atherosclerosis, small vessel disease and cardioembolic stroke (CE), as clas ...[more]
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Project description:Background. Genetic risk scores (GRS), summing up the total effect of several single nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS, based on 29 SNPs discovered by genome-wide association studies (GWAS) and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other “traditional risk factors”, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study. Methods and results. Twenty-nine SNPs were genotyped in 3,677 stroke cases and 2,415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the entire material, and separately for the three samples. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the entire material [OR (95% CI) 1.086 (1.029-1.147) per SD increase in the GRS p=0.003] with similar trends in all three samples; LSR [1.050 (0.967-1.140)]; p=0.25], MDC [1.168 (1.060-1.288); p=0.002] and SAHLSIS [1.124 (0.997-1.267); P=0.055]. Measures of discrimination and reclassification improved marginally using the GRS. Conclusions. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case-control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.
| EGAS00001000936 | EGA
Project description:Two common polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012 (approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group (P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke (OR = 1.844, 95% CI: 1.286-2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke (OR = 1.366, 95% CI: 1.077-1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype (OR = 2.953, 95% CI: 2.082-4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction (OR = 3.404, 95% CI: 1.631-7.102, P < 0.001) and additive interaction (RERI = 41.705, 95% CI: 14.586-68.824, AP = 0.860; 95% CI: 0.779-0.940; S = 8.170, 95% CI: 3.772-17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele (OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele (OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.
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Project description:BackgroundThe association between socioeconomic status (SES) and stroke risk remains controversial around the world. It is not clear that the effect of SES on stroke in China due to the lack of relevant research. We aimed to assess the association between SES and risks of first-ever ischemic stroke in Guangzhou, China.MethodsCases were recruited from neurology department in the First Affiliated Hospital of Guangdong Pharmaceutical University during September 2016-October 2017. Age- and sex-matched controls were derived from surgical departments, over the same period. SES was assessed based on education, occupation, and income. Education was divided into ≤6 years, 6-9 years, 10-12 years, and > 12 years. Family monthly income per capita was categorized into ≤¥1000, ¥1001-3000, ¥3001-5000, and > ¥5001. Occupation was stratified into manual, non-manual, no job, and retired. A multivariate logistic regression model was used to determine the association between SES and risk of ischemic stroke.ResultsIn total, 347 ischemic stroke patients and 347 controls were recruited, with mean ages of 60.54 ± 13.13 and 60.56 ± 13.07 years, respectively. After adjusting for confounding factors, odds ratio (OR) for 6-9 years of education was 2.63 (95% confidence interval [CI] 1.45-4.75); > 12 years, 2.18 (1.25-3.82) compared with those for < 6 years of education. ORs for the second lowest, third lowest, and highest incomes were 1.96 (1.21-3.15), 4.16 (2.39-7.22), and 2.83(1.25-6.39), respectively, compared with those for the lowest income. ORs for manual workers and non-manual workers were 1.95 (1.23-3.07) and 1.87 (1.05-3.33), compared with individuals without jobs.ConclusionsHigher SES is positively related with risks of ischemic stroke, explained by cardiovascular diseases and unhealthy lifestyles in Guangzhou, China. Thus, effective strategies such as extensive health education, promoting a healthy lifestyle, screening for risk factors to prevent stroke should be implemented to reduce ischemic stroke incidences among the high SES group.
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Project description:Background Recent studies have shown an increasing prevalence of vascular risk factors in young adults with ischemic stroke ( IS ). However, the strength of the association between all vascular risk factors and early-onset IS has not been fully established. Methods and Results We compared 961 patients with a first-ever IS at 25 to 49 years to 1403 frequency-matched stroke-free controls from a population-based cohort study ( FINRISK ). Assessed risk factors included an active malignancy, atrial fibrillation, cardiovascular disease, current smoking status, a family history of stroke, high low-density lipoprotein cholesterol, high triglycerides, low high-density lipoprotein cholesterol, hypertension, and type 1 and type 2 diabetes mellitus. We performed subgroup analyses based on age, sex, and IS etiology. In a fully adjusted multivariable logistic regression analysis, significant risk factors for IS consisted of atrial fibrillation (odds ratio [OR], 10.43; 95% confidence interval [ CI ], 2.33-46.77], cardiovascular disease (OR, 8.01; 95% CI , 3.09-20.78), type 1 diabetes mellitus (OR, 6.72; 95% CI , 3.15-14.33), type 2 diabetes mellitus (OR, 2.31; 95% CI , 1.35-3.95), low high-density lipoprotein cholesterol (OR, 1.81; 95% CI , 1.37-2.40), current smoking status (OR, 1.81; 95% CI , 1.50-2.17), hypertension (OR, 1.43; 95% CI , 1.17-1.75), and a family history of stroke (OR, 1.37; 95% CI , 1.04-1.82). High low-density lipoprotein cholesterol exhibited an inverse association with IS . In the subgroup analyses, the most consistent associations appeared for current smoking status and type 1 diabetes mellitus. Conclusions Our study establishes the associations between 11 vascular risk factors and early-onset IS , among which atrial fibrillation, cardiovascular disease, and both type 1 and 2 diabetes mellitus in particular showed strong associations.
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Project description:Background and objectives: Siesta, which is a short afternoon nap, is a habit that is commonly practiced in the Mediterranean and tropical areas. Data on the association between siesta and coronary artery disease has been conflicting. A protective effect has been demonstrated in the countries that commonly practice siesta, but a harmful effect has been observed in the countries that infrequently practice the siesta habit. Information on the association between siesta and ischemic stroke has been, however, lacking. Hence, the purpose of our study was to determine the effect of siesta on ischemic stroke. Materials and Methods: This was a case-control study, conducted on the patients with acute ischemic stroke who came for their first follow-up visit to the neurology clinic. Controls were randomly selected from the patients visiting the neurology clinic on the same day as the patients with ischemic stroke. In addition to basic demographics and the occurrence of established stroke risk factors, information about siesta practice was also collected from both groups. A multivariate logistic regression analysis was utilized to determine the relationship between siesta practice and ischemic stroke. Results: A total of 206 patients were recruited from the neurology clinic of King Khalid university hospital; of which only 194 subjects were included in the analysis (98 ischemic stroke cases and 96 controls). The mean age of the participants was 59.68 ± 13.75 years and 98 (50.52%) were male. Interestingly, 43% of the whole study cohort practiced regular siesta. However, when compared to the stroke population, the control group practiced siesta more frequently (30% vs. 56%). In a multivariate logistic regression analysis, hypertension, diabetes mellitus, excess body weight (body mass index > 25 kg/m2) and dyslipidemia were found to increase the risk of ischemic stroke (OR 2.12, 95% CI: 1.02-4.66, p = 0.005; OR 2.72, 95% CI: 1.94-4.88, p = 0.014; OR 2.94, 95% CI: 1.5164-5.7121 p = 0.0014; OR 3.27, 95% CI: 2.42-5.199, p ? 0.001, respectively). On the contrary, the practice of regular siesta lowered the risk of ischemic stroke (OR 0.58, 95% CI: 0.3551-0.9526, p = 0.031). Conclusions: Siesta was associated with a reduced risk for the occurrence of ischemic stroke. Large prospective longitudinal studies should be conducted to verify the protective effect of siesta on stroke.
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Project description:Ischemic stroke is a complicated disease, and its pathogenesis has been attributed to the occurrence of genetic polymorphisms. Evidence has suggested that the microRNA let-7a is involved in the pathogenesis of ischemic stroke. Pri-miRNA is the primary transcript, which undergoes several processing steps to generate pre-miRNA and, later, mature miRNAs. In this case-control study, we analyzed the distribution of pri-let-7a-2 variants in patients at a high risk for ischemic stroke and the interactions of pri-let-7a-2 variants and environmental factors. Blood samples and clinical information were collected from 1086 patients with ischemic stroke and 836 healthy controls between December 2013 and December 2015 at the First Affiliated Hospital of China Medical University. We found that the rs1143770 CC genotype and the C allele were associated with a decreased risk of ischemic stroke, whereas the rs629367 CC genotype was associated with an increased risk for ischemic stroke. Moreover, these two single-nucleotide polymorphisms were in linkage disequilibrium in this study sample. We analyzed gene-environment interactions and found that rs1143770 exerted a combined effect on the pathogenesis of ischemic stroke, together with alcohol use, smoking, and a history of hypertension. Therefore, the detection of pri-let-7a-2 polymorphisms may increase the awareness of ischemic stroke risk. This study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of China Medical University, China (approval No. 2012-38-1) on February 20, 2012, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559) on December 27, 2017.
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Project description:This study aimed to assess the association of APO gene polymorphisms and ischemic stroke risk in a Chinese Han population. In this case-control study, we genotyped 14 single nucleotide polymorphisms (SNPs) in 3 APO genes in 488 cases and 503 controls using Sequenom Mass-ARRAY technology and evaluated their association with ischemic stroke using the ?2 and genetic model analysis. In the allelic model analysis, we determined three SNPs were significantly associated with ischemic stroke: rs693 with a p value of 0.042 (OR = 1.406; 95%CI = 1.011-1.956), rs651821 with a p value of 0.007 (OR = 0.760; 95%CI = 0.622-0.929) and rs662799 with a p value of 0.006 (OR = 0.755; 95%CI = 0.618-0.923). In the genetic model analysis, we found the minor allele "A" of rs693 was associated with an increased ischemic stroke risk in the additive model and dominant model. The minor allele "C" of rs651821 was associated with a decreased ischemic stroke risk in the additive model. The minor allele "G" of rs662799 was associated with a decreased ischemic stroke risk in the additive model. Additionally, strong linkage was found in 3 blocks constituted by rs1042034, rs676210, rs693, rs673548 in APOB; rs3791981, rs679899 in APOB; and rs651821, rs662799, rs17120035 in APOA5. Our data suggested that gene polymorphisms in the APO genes may exert influences ischemic stroke susceptibility in a Chinese Han population.
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Project description:Genetic risk scores (GRS), summing up the total effect of several single-nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS based on 29 SNPs discovered by genome-wide association studies and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other 'traditional risk factors', also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study. Twenty-nine SNPs were genotyped in 3677 stroke cases and 2415 controls included in the Lund Stroke Register (LSR), the Malmö Diet and Cancer (MDC) study and the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The analysis was conducted in the combined sample, and separately for the three studies. After adjustment for hypertension, diabetes mellitus and smoking habits, the GRS was associated with ischemic stroke in the combined sample (OR (95% CI) 1.086 (1.029-1.147) per SD increase in the GRS P=0.003) with similar trends in all three samples: LSR (1.050 (0.967-1.140); P=0.25), MDC (1.168 (1.060-1.288); P=0.002) and SAHLSIS (1.124 (0.997-1.267); P=0.055). Measures of risk discrimination and reclassification improved marginally using the GRS. A blood pressure GRS is independently associated with ischemic stroke risk in three Swedish case-control studies, however, the effect size is low and adds marginally to prediction of stroke on top of traditional risk factors including hypertension.
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