Single nucleotide polymorphism of CD40 in the 5′-untranslated region is associated with ischemic stroke

Objectives

Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods

We conducted a case–control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results

Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR = 1.273, 95% CI = 1.016–1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR = 2.350, 95% CI = 1.601–3.449; for TT/CT: OR = 2.148, 95% CI = 1.479–3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR = 6.538, 95%CI = 1.655–25.833; for TT/CT: OR = 3.469, 95%CI = 1.031–11.670), respectively.

Conclusions

The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.     

进展性卒中血同型半胱氨酸变化的相关研究

目的:了解各型SIP患者Hcy浓度改变特点的同时,更深一层地探讨各型进展性卒中病情变化与血Hcy水平的关系.方法:抽取SIP组、SIS组脑卒中患者各50名,发病第1,2,3天清晨空腹肘静脉血5mL,采用全自动快速分析仪及其配套Hcy试剂盒,用荧光偏振免疫法测定血浆总Hcy水平.结果:不论是进展性脑卒中还是稳定性脑卒中,与正常相比,Hcy的水平要高于正常组,差异具有显著性,P＜0.01;同时进展性脑卒中与稳定性脑卒中相比较而言,进展性脑卒中的Hcy水平显著高于稳定性脑卒中,P＜0.05.结论:SIP患者Hcy水平显著高于稳定性脑卒中,Hcy增高可能是SIP发展的一个标志.     

血清CysC、hs-CRP与急性脑梗死分型及并发医院感染的相关性探究

摘要 目的：探究血清胱抑素C（CysC）、超敏C反应蛋白（hs-CRP）与急性脑梗死TOAST分型及并发医院感染的相关性。方法：以2017年9月~2022年9月84例急性脑梗死患者（脑梗死组）及57例健康体检者（对照组）为研究对象，采用免疫比浊法检测受试者血清CysC水平，采用乳胶增强免疫比浊法检测其hs-CRP水平。分析血清CysC、hs-CRP水平与急性脑梗死TOAST分型及并发医院感染的关系。结果：本研究纳入病例中无不明原因性缺血性卒中（SUE）患者，主要包括大动脉粥样硬化型（LAA）患者37例、小动脉闭塞型（SAO）患者12例、心源性栓塞型（CE）患者31例、其他病因明确型缺血性卒中（SOE）患者4例。不同TOAST分型患者的血清CysC、hs-CRP水平对比，存在显著性差异（P<0.05）；CE组血清CysC、hs-CRP水平高于LAA组、SAO组、SOE组，LAA组血清CysC、hs-CRP水平高于SAO组、SOE组，SAO组血清CysC、hs-CRP水平高于SOE组（P<0.05）。根据NIHSS评分将脑梗死患者分为重度组18例、中度组29例、轻度组37例，不同严重程度脑梗死患者的血清CysC、hs-CRP水平均高于对照组，且重度组高于中度组、轻度组（P<0.05）；中度组的血清CysC水平高于轻度组（P<0.05）。血清CysC、hs-CRP水平与脑梗死患者NIHSS评分均呈正相关（P<0.05）。84例脑梗死患者伴发医院感染28例，其中上呼吸道感染13例、肺部感染8例、泌尿系统感染5例、其他2例。感染组中合并糖尿病、有侵入性操作、TOAST分型为CE型的人数比例高于未感染组，NIHSS评分及血清CysC、hs-CRP水平高于未感染组（P<0.05）。侵入性操作、NIHSS评分≥16分、TOAST分型为CE型及CysC、hs-CRP水平升高是急性脑梗死并发感染的危险因素（P<0.05）。结论：CE型急性脑梗死患者血清CysC、hs-CRP水平显著升高，与病情严重程度相关，且侵入性操作、NIHSS评分≥16分、TOAST分型为CE型及CysC、hs-CRP水平升高是急性脑梗死并发感染的危险因素。     

Applying DNA barcodes for identification of plant species in the family Araliaceae

Genetic variants of tPA (PLAT) and PAI-1 genes have been suggested to be the risk factors for stroke. In the present case-control study we investigated the association of − 7351 C/T polymorphism (rs2020918) and I/D polymorphism of tPA gene and Insertion/deletion polymorphism (4 G/5 G) of PAI-1 gene with genetic predisposition to ischemic stroke. 516 stroke patients and 513, sex and age matched healthy controls were involved in the study. We did not find a significant association of tPA − 7351 C/T polymorphism and PAI-1 4 G/5 G polymorphism with stroke. However, in case of I/D polymorphism significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. DD genotype and D allele associated significantly with stroke (p = 0.002 and < 0.001 respectively). We also found significant association of I/D polymorphism with intracranial large artery atherosclerosis and stroke of undetermined etiology. Exploring the association between gene-gene interaction (26 combinations including the three variants) and stroke, we found that individuals with CC + 4G4G + DD, CC + 5G5G + ID, CT + 4G5G + ID, CT + 5G5G + II, CT + 5G5G + ID and TT + 4G5G + II had a significantly higher risk of stroke. The results of this study suggest that − 7351 C/T polymorphism of tPA and 4 G/5 G polymorphism of PAI-1 are not associated with stroke, while as DD genotype and D allele of tPA gene are important risk factors for ischemic stroke. Further we found that the subjects with different tPA and PAI genotype combinations displayed a significantly high risk for overall ischemic stroke suggesting that gene-gene interaction involving more variants may change the susceptibility of particular subjects to the disease.     

Flavin containing monooxygenase 3 genetic polymorphisms Glu158Lys and Glu308Gly and their relation to ischemic stroke

Ischemic stroke is a multifactorial disease leading to severe long-term disability and it is the third leading cause of death in developed countries. Although many studies have been reported to elucidate etiological and pathological mechanisms of stroke, the genetic and molecular basis of disease remains poorly understood. Recent studies have shown that reactive oxygen species causing oxidative stress play a pivotal role in the pathogenesis of atherosclerosis that is the main cause of a group of cardiovascular diseases including ischemic stroke. In this study, we aimed to investigate the relationship between FMO3 Glu158Lys and Glu308Gly variants, and the risk of incidence of ischemic stroke in Turkish population. Two single nucleotide polymorphisms (SNPs) within the FMO3 gene were genotyped by using PCR-RFLP technique in a sample set of 245 cases and 145 controls. In the case-control analysis, no significant difference was observed between stroke patients and controls with respect to FMO3 Glu158Lys and Glu308Gly polymorphisms' genotype and allele frequency distribution. However, heterozygote 158Glu/Lys (OR = 6.110, P < 0.001) and 308Glu/Gly (OR = 6.000, P = 0.006) genotypes increase the risk of stroke 6 times in hypertensive subjects. On the other hand, the wild type genotypes 158Glu/Glu and 308Glu/Glu had 6.2-fold and 4.8-fold higher risk of ischemic stroke in obese subgroup, respectively. Our results clearly showed that the risk of hypertension-related ischemic stroke was higher in the heterozygote genotype carriers. This is the first study conducted regarding the association of FMO3 Glu158Lys and Glu308Gly genetic polymorphisms and ischemic stroke risk in Turkish population.     

Association of SNP41, SNP56 and a novel SNP in PDE4D gene with stroke and its subtypes

An association between phosphodiesterase 4D (PDE4D) gene and risk of stroke has been suggested by deCODE group in an Icelandic population. In the present case–control study we investigated the association of SNP41 (rs12153798) and SNP56 (rs702553) with ischemic stroke and stroke subtypes. Five hundred and sixteen ischemic stroke patients and 513 healthy age and sex matched controls were included in the study. The genotypes were determined by subjecting the PCR products to sequencing. Both the SNPs 56 and 41 associated significantly with stroke [adjusted OR = 1.97; 95% CI (1.262–3.082); p = 0.003: adjusted OR = 5.42; 95% CI (3.45–8.5); p < 0.001 respectively]. In addition to this, a novel SNP at position 59736747 T > G was found while sequencing the PCR products including SNP56. This novel SNP was found in patients as well as controls but did not show a significant association with the disease. We found significant association of SNPs 56 and 41 with large artery atherosclerosis, lacunar and cardioembolic stroke. In conclusion PDE4D gene plays a key part in the pathogenesis of ischemic stroke in the South Indian population from Andhra Pradesh.     

Association of IL-6 − 174G > C and − 572C > G polymorphisms with risk of young ischemic stroke patients

Aim

To investigate the association between interleukin-6 (IL-6) − 174G > C and − 572C > G polymorphisms and risk for ischemic stroke (IS) in young patients.

Methods

We genotyped IL-6  − 174G > C and − 572C > G in a case–control study of 430 young IS patients and 461 control subjects. An unconditional multiple logistical regression model was used to calculate the effects of IL-6 − 174G > C and − 572C > G polymorphisms on IS risk.

Results

Higher body mass index, diabetes, hypertension, obesity, and smoking were associated with risk of ischemic stroke. Multivariate regression analyses showed that subjects carrying the − 174CC genotype (OR = 1.69, 95% CI = 1.16–2.57) and C allele (OR = 1.37, 95% CI = 1.09–1.67) had a small but significant increased risk of IS. Similarly, those carrying the − 572GG genotype (OR = 2.12, 95% CI = 1.18–3.82) and G allele (OR = 1.43, 95% CI = 1.14–1.83) had a moderate increased risk of IS. We found the − 174G > C and − 572C > G polymorphisms interact with hypertension and obesity.

Conclusion

Our results suggest that polymorphisms in IL-6 − 174G > C and − 572C > G are associated with IS risk in young patients, and that these polymorphisms interact with hypertension, obesity and etiologic subtypes. These findings could be helpful in identifying individuals at increased risk for developing IS.