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Background: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population. Methods: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool. Results: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR = 0.76, 95% CI = 0.58-0.99 and OR = 0.76, 95% CI = 0.58-0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR = 0.63, 95% CI = 0.45-0.88), no hypertension (OR = 0.66, 95% CI = 0.46-0.94), diabetes (OR = 0.33, 95% CI = 0.17-0.64), and smoking (OR = 0.65, 95% CI = 0.44-0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR = 4.48; 95% CI = 2.98-6.72) increased risk of AS. Conclusion: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population. [ABSTRACT FROM AUTHOR]

Elevated C-reactive protein (CRP) levels increase the risk of poor functional disability in patients with ischemic stroke (IS). This study aimed to investigate the association between CRP gene polymorphisms and 3-month functional disability of large artery atherosclerotic (LAA) stroke in Han Chinese. Patients with first-ever LAA IS were prospectively enrolled in Nanjing Stroke Registry Program between August 2013 and October 2015. Five single-nucleotide polymorphisms (SNPs) (rs876537, rs2794520, rs3093059, rs7553007 and rs11265260) in CRP gene related to CRP levels in Asian by genome-wide association study were genotyped. The functional outcome at 3 months after the index stroke was assessed by the modified Rankin scale. Associations between genotypes and functional outcome of LAA IS were analyzed with logistic regression model. A total of 690 eligible patients (507 males) were evaluated. SNPs rs11265260 (multivariate-adjusted, p = 0.022), rs2794520 (multivariate-adjusted, p = 0.036) and rs3093059 (multivariate-adjusted, p = 0.027) were significantly associated with elevated CRP in acute IS. Two SNPs, rs3093059 (dominant model: adjusted OR 2.49; 95% CI 1.55-4.00; recessive model: adjusted OR 3.67; 95% CI 1.22-11.03) and rs11265260 (dominant model: adjusted OR 2.51; 95% CI 1.56-4.02; recessive model: adjusted OR 4.70; 95% CI 1.63-13.56) independently predicted 3-month poor outcome of first-ever LAA IS, after adjusting for covariates. In addition, haplotype analysis indicated that haplotype GCTGC (adjusted OR 1.76; 95% CI 1.05-2.95; p = 0.031) increased the poor outcome risk. SNPs rs3093059 and rs11265260 in CRP gene may influence the 3-month functional outcome of first-ever LAA IS in Han Chinese. [ABSTRACT FROM AUTHOR]

Background: In 2009, a genome-wide association study (GWAS) identified two variants (rs12425791 and rs11833579) nearNINJ2gene that confer susceptibility to stroke in Caucasian populations. Recently, a number of studies have been conducted to replicate this finding in Asian populations. However, the results are conflicting. Thus, we performed a quantitative analysis to summarize the evidence regarding the association between these two polymorphisms and ischemic stroke risk.Methods: Pertinent studies were identified by searching PubMed and Embase through September 2014. Studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between these two polymorphisms and stroke risk were included.Results: Eight independent publications, with 8626 cases and 8046 controls for rs12425791 and 9142 cases and 8657 controls for rs11833579, were included. Overall, significantly increased ischemic stroke risk was associated with rs12425791 A allele when all studies were pooled into the meta-analysis (AA/GA vs. GG: OR = 1.08, 95% CI: 1.01–1.14). However, rs11833579 was not associated with increased stroke risk in any genetic model.Conclusions: These findings indicate that rs12425791 G>A polymorphism may be a low-penetrance susceptibility marker of stroke in Asian populations and further studies are warranted to verify this association. [ABSTRACT FROM AUTHOR]

Recently, a genome-wide association study (GWAS) identified two common variants (rs12425791 and rs11833579) on Chromosome 12p13 that confer risk for stroke. The aim of this study was to evaluate whether these two variants are associated with risk of large artery atherosclerotic (LAA) stroke in a Chinese population. Rs12425791 and rs11833579 were genotyped using the improved multiple ligase detection reaction in 423 patients with LAA stroke and 423 healthy controls. We found a statistically significantly increased risk of LAA stroke associated with the rs12425791AA genotype (OR = 2.28, 95% CI = 1.15–4.51) and rs11833579 AA genotype (OR = 1.92, 95% CI = 1.16–3.15) compared with their GG genotype. When we evaluated these two polymorphisms together, we found that the combined genotypes with 3–4 variant alleles (rs12425791A and rs11833579A) were associated with an increased risk of LAA stroke (OR = 2.06, 95% CI = 1.26–3.36) compared to 0–2 variants. Moreover, genotype–phenotype correlation analysis showed that rs12425791AA and rs11833579AA carriers had significantly decreased NINJ2 mRNA expression levels in the Chinese population ( P = 0.003 for rs12425791 and P = 0.005 for rs11833579). These results suggested that the rs12425791 and rs11833579 polymorphisms on Chromosome 12p13 may be associated with the risk of LAA stroke and might be used as candidate biomarkers for LAA stroke susceptibility. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation and nucleotide synthesis. Accumulated evidence has demonstrated that C677T and A1298C polymorphisms of the MTHFR gene are associated with acute lymphoblastic leukemia (ALL) risk, but the results have been inconclusive. To determine a more precise estimation, we performed a meta-analysis of 28 studies with 4240 cases and 9289 controls. We found that the 677TT genotype showed a reduced risk of ALL compared with the 677CC genotype in the overall population (odds ratio [[OR]] 0.76, 95%% confidence interval [[CI]] 0.61-0.92). The reduced risk was pronounced only among the Caucasian population (OR 0.68, 95%% CI 0.51-0.90), not the Asian (OR 0.89, 95%% CI 0.75-1.05). For the MTHFR A1298C polymorphism, no significant association with ALL susceptibility was observed in the pooled analyses. However, significantly increased ALL risk was found in childhood inthe comparison of 1298CA versus AA genotype. This study provides evidence that MTHFR polymorphisms may play animportant role in the development of ALL. [ABSTRACT FROM AUTHOR]

Abstract Background and aims A recent genome-wide association study (GWAS) reported an association between a single nucleotide polymorphism (SNP) rs11196288 and risk of early-onset large artery atherosclerotic (LAA) stroke in European population. The interaction between genetic and environmental factors such as age has also received increasing attention. We performed this study to investigate the association between the rs11196288A > G polymorphism and LAA stroke risk in the Chinese Han population and test whether age interacts rs11196288 to influence LAA stroke risk. Methods Genotyping of rs11196288 was performed in 1066 LAA stroke patients and 1167 healthy controls. Multivariate logistic regression analyses were applied to assess the effect of the rs11196288A > G polymorphism on susceptibility and short-term outcome of LAA stroke. Nomograms were performed to estimate probability of risk for an individual patient. Results A significant decrement of LAA stroke risk was found in co-dominant (AG vs. AA, OR = 0.76, 95% CI = 0.64–0.91, P = 0.003; GG vs. AA, OR = 0.65, 95% CI = 0.50–0.85, P = 0.002), dominant (AG/GG vs. AA, OR = 0.74, 95% CI = 0.62–0.87, P < 0.001) and recessive models (GG vs. AA/AG, OR = 0.76, 95% CI = 0.59–0.97, P = 0.028) of rs11196288. However, the interaction between age and genotypes of rs11196288 was not statistically significant, and no significant association was observed between the rs11196288A > G polymorphism and short-term outcome of LAA stroke (P > 0.05). Conclusions In the southeastern Chinese population, the rs11196288A > G polymorphism is associated with decreased risk of LAA stroke. Highlights • Individuals with rs11196288 G allele have lower risk of LAA stroke. • The association between rs11196288 and LAA stroke risk varies among different age groups. • The rs11196288 is not a predictor of short-term outcome of LAA stroke. • Nomograms were performed to estimate probability of risk for an individual patient. [ABSTRACT FROM AUTHOR]

• rs2073617 or rs3134069 are associated with risk of poor outcome of LAA stroke. • The rs2073618 is not associated with risk of short-term poor outcome of LAA stroke. Osteoprotegerin is involved in the progression of atherosclerosis. This study aimed to determine whether TNFRSF11B polymorphisms are associated with prognosis of large artery atherosclerosis (LAA) stroke. Three TNFRSF11B polymorphisms (rs2073617, rs2073618 and rs3134069) were genotyped in 1010 patients with LAA stroke. Short-term outcome was evaluated using the modified Rankin Scale score at 3-month after stroke onset. Long-term outcome was assessed using the stroke recurrence. We found that rs2073617G was associated with an increased risk of poor outcome of LAA stroke (additive model: odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.06–1.73). This association was also observed in rs3134069C (additive model: OR = 1.53, 95% CI = 1.10–2.12). Furthermore, when we combined these two polymorphisms according to the numbers of risk alleles (rs2073617G and rs3134069C), we found that the patients with 3–4 risk alleles were statistically significantly associated with an increased risk of poor outcome of LAA stroke (OR = 1.90, 95% CI = 1.10–3.28) compared with 0–2 risk alleles, and this increased risk was more evident among those with hypertension (OR = 2.02, 95% CI = 1.04–3.91), those without diabetes (OR = 2.02, 95% CI = 1.02–4.01) and those with smoking (OR = 2.43, 95% CI = 1.09–5.42). In silico analysis showed that rs2073617 and rs3134069 are located in various histone modification marked regions, DNase I hypersensitive sites and can change the binding of regulatory motifs. Moreover, rs2073617 is also located in the binding site of transcription factors. Our findings suggested that TNFRSF11B polymorphisms may be associated with an increased risk of short-term poor outcome of LAA stroke. [ABSTRACT FROM AUTHOR]