Qidong Yang

Incidence of Cerebral Hemorrhage in the Changsha Community

Background and Purpose: Intracranial hemorrhage (ICH) constitutes an important subtype of stroke. In a prior study, we found that the city of Changsha, People’s Republic of China, not only had a high incidence of stroke, but also had almost the highest incidence of cerebral hemorrhage. To provide information for preventing and managing ICH, we undertook this study supervising and determining the annual first-ever average incidence of cerebral hemorrhage from 1986 to 2000 in Changsha. Methods: In January 1986, people from 6 well-defined communes in the Kai-fu district in Changsha were selected as the study population. Since 1991, we added another 18 well-defined communes of the same district. Data on these residents were obtained from the census register of the local administrative office. Persons who had a history of stroke were excluded from our study at the beginning. Every year, we checked up on the population and carried out door-to-door inquiries to verify the new cases of ICH and stroke. If the patients were diagnosed in hospital, as many as possible were examined with CT and/or MRI. The incidence rate adjusted to the World population in 1985 for age and sex, as well as the prevalence of risk factors were calculated. Results: An accumulative total of 551,163 people were supervised in 15 years (from 1986 to 2000); the annual average incidences of stroke and ICH were 236.6/100,000 (adjusted rate: 154.7) and 131.0/100,000 (adjusted rate: 73.1), respectively. From 1986 to 2000, the total annual average rate of stroke confirmed by CT and/or MRI in Changsha was 70.8%, and for ICH it was 64.7%. The incidences of stroke and ICH confirmed by image analysis were 167.5 (adjusted rate: 110.8) and 84.7 (adjusted rate: 55.1), respectively. The mean annual mortality rate of ICH was 78.3/100,000 (adjusted rate: 49.3) and that of stroke was 124.5/100,000 (adjusted rate: 97.0). The percentage of ICH among stroke cases was 55.4%. Among patients with ICH, 79.8% had hypertension, 30.6% had cardiovascular disease, 7.6% had diabetes mellitus, and 12.5% had an abnormal high level of lipid. Among patients with other subtypes of stroke apart from ICH, the percentages were 76.6, 40.6, 15.5, and 22.5%. Conclusions: The incidence of ICH in Changsha is very high, so is the proportion of ICH among all stroke cases. Changsha is an area with a high incidence of ICH in the world. Hypertension is the prominent risk factor. The study demonstrated the importance of ICH as a significant subtype of stroke.

Detection of platelet microRNA expression in patients with diabetes mellitus with or without ischemic stroke

AIMS The objective of this study was to investigate the role of plasma and platelet microRNAs in the occurrence of ischemic stroke in patients with diabetes mellitus. METHODS miR-223, miR-146a, miR-495, and miR-107 expression in the plasma and platelets, blood glucose concentration, and platelet activation rate were measured in patients with diabetes mellitus and ischemic stroke, diabetes mellitus only, ischemic stroke only, and healthy controls. Platelet activity was measured by flow cytometric measurement of P-selectin expression, while miRNA was measured by real-time PCR. RESULTS The expressions of platelet and plasma miR-223 and miR-146a were significantly downregulated in patients with ischemic stroke and diabetes mellitus or diabetes mellitus only, but not in patients with ischemic stroke only compared to healthy controls. The expressions of platelet and plasma miR-495 and miR-107 showed no significant differences among these four groups. The expression of platelet miR-223 and miR-146a significantly correlated with plasma miR-223 and miR-146a levels, blood glucose concentration, and platelet activation rate. CONCLUSIONS Hyperglycemia may downregulate the expressions of miR-223 and miR-146a, leading to subsequent platelet activation in patients with diabetes mellitus. Low platelet and plasma miR-223 and miR-146a expression is a risk factor for ischemic stroke in Chinese diabetes mellitus patients.

Changes in hippocampal synapses and learning-memory abilities in a streptozotocin-treated rat model and intervention by using fasudil hydrochloride

Fasudil hydrochloride (FH), a Rho kinase inhibitor, is used to treat neurological diseases. This study aims to elucidate the anti-dementia role of FH in Alzheimers disease. Twenty-four Sprague-Dawley rats were randomly divided into four groups: (1) sham-operated group (control), (2) sham-operated followed by FH administration group (sham+FH), (3) streptozotocin (STZ)-treated group (STZ), and (4) STZ treatment followed by FH administration group (STZ+FH). Rats in the STZ and STZ+FH groups received two divided doses of STZ (1.5 mg/kg) intracerebroventricularly on days 1 and 3, whereas control and sham+FH group rats were given citric acid/sodium citrate buffer. Rats in the sham+FH and STZ+FH groups were then treated intraperitoneally with FH (10 mg/kg) for 4 weeks, and rats in the STZ and control groups were treated with saline. Learning and memory were measured using the Morris water maze test. The synaptic ultrastructure in the CA1 region of the hippocampus was observed using electronic microscopy. The expression of synaptophysin (SYP) was measured using real-time polymerase chain reaction and western blot analyses; the expression of p-LIMK2 and p-cofilin were also detected using western blot analysis. The results indicate that STZ induced deficit in learning/memory, decrease in SYP expression, degeneration in synaptic structures, and increase in the expressions of p-LIMK2 and p-cofilin. These changes were reversed by the administration of FH, suggesting that FH has anti-dementia properties that protect synaptic structure and function. FH induced dephosphorylation (inactivation) of LIMK2 and subsequent dephosphorylation (activation) of cofilin, which may be responsible for the amelioration of neuronal synaptic structure and function.

Lack of the Toll-Like Receptor 4 Gene Polymorphisms Asp299Gly and Thr399ile in a Chinese Population

ABSTRACT The toll-like receptor 4 (TLR4), predominantly known for its role as an important mediator of immune reactions, is expressed in atherosclerotic lesions. Atherosclerosis resulting in cerebral or carotid arterial stenosis/occlusion plays the most important role in the occurrence of cerebral infarction (CI), and thus TLR4 polymorphisms may influence formation of atherosclerosis and the development of CI. This study was aimed to detect two commonly reported Asp299Gly and Thr399Ile polymorphisms in TLR4 gene in Hunan Han Chinese and their possible relationship with CI. By using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the polymorphisms TLR4, Asp299Gly and Thr399Ile, were determined in 366 CI patients and 200 controls from Changsha area of Hunan Province. Carotid intima-media thickness (CIMT) also was detected by Bmode ultrasonography. Our results suggested both the TLR4, Asp299Gly and Thr399Ile, genetic polymorphisms were not observed in all subjects from Hunan Changsha. Therefore, we speculate they might not be an important factor in the development of CI in the Chinese.

Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population

Abstract Objectives: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population. Methods: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software. Results: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed. Discussion: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.

Apolipoprotein H Gene Polymorphisms and Risk of Primary Cerebral Hemorrhage in a Chinese Population

Background and Purpose: Apolipoprotein H (ApoH) has been implicated in several physiologic pathways including lipid metabolism, coagulation and the production of hypertension, which are related to the pathogenesis of primary cerebral hemorrhage (PICH). The gene coding for ApoH is polymorphic, with the occurrence of several common alleles in the general population. This genetically determined variation can effect lipid metabolism and the production of hypertension. We determined the distribution of ApoH gene polymorphisms in Chinese people and investigated whether these polymorphisms were associated with increased risk of PICH in a Chinese population. Methods: We studied polymorphisms of the ApoH gene by the polymerase chain reaction-single strand conformation polymorphism technique and DNA sequencing in 140 PICH patients and 100 healthy control subjects. Serum antiphospholipid antibodies and lipid levels were also examined in all subjects. Results: Four polymorphisms of the ApoH gene have been identified in Chinese people. No difference in genotype frequencies of G817T (Leu247Val) polymorphism, G1025C (Try316Ser) polymorphism and C1080T polymorphism was observed between PICH patients and control subjects (p > 0.05). The G341A (Ser88Asn) polymorphism correlated significantly with PICH. The frequencies of the A allele were significantly higher in PICH patients than in controls, especially in PICH patients with hypertension and a family history of stroke. Conclusions: Our results suggest that the G341A (Ser88Asn) polymorphism might be associated with increased risk of PICH in a Chinese population. The association appeared to be mediated by the generation of hypertension.

Association study between C7673T polymorphism in apolipoprotein B gene and cerebral infarction with family history in a Chinese population.

BACKGROUND Apolipoprotein B (ApoB) levels have been shown to be associate with risk of ischemic stroke. The apolipoprotein B gene (APOB) polymorphisms may influence levels of ApoB and risk of ischemic stroke, but whether they are associated with risk of ischemic cerebral infarction (CI) with family history (CIFH) or not is unknown. AIMS To investigate the possible association of the polymorphism of APOB C7673T with CIFH in Han Chinese from Changsha. SETTINGS AND DESIGN The study population included 47 patients with CIFH and 83 patients with cerebral infarction with no family history (CINFH). Control population included 100 healthy subjects with no history of ischemic stroke matched for age, sex, and ethnic background. MATERIALS AND METHODS The APOB C7673T polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma lipids levels were also examined by standard enzymatic methods and enzyme-linked immunosorbent assay (ELISA). STATISTICS The statistical analysis was done using SPSS 14.0 software package. A P value < 0.05 was taken as significant. RESULTS This study showed an association between the APOB C7673T polymorphism and CI, especially CIFH in Han Chinese from Changsha. The T alleles frequency of the C7673T polymorphism was significantly higher in both the CIFH and CINFH groups when compared with the control group (P < 0.01; P < 0.05; respectively). And the T allele frequency in CIFH group (0.17) was higher than CINFH (0.09) group (P = 0.056). In both the CIFH and CINFH groups the serum levels of TC and LDL cholesterol were significantly high in the TT and TC genotypes than that in the CC genotype (P < 0.01), while the serum level of HDL cholesterol in the TT and TC genotypes was significantly lower than that in the CC genotype (P < 0.05). CONCLUSIONS The APOB C7673T polymorphism is related to CI, especially CIFH through changing serum lipid levels in a Chinese population.

Association of PTEN genetic polymorphisms with atherosclerotic cerebral infarction in the Han Chinese population

The phosphatase and tensin homologue (PTEN) gene is critical to the pathological development of atherosclerosis, a major risk factor for atherosclerotic cerebral infarction (ACI). However, it remains unclear whether genetic polymorphism in the PTEN gene can affect the risk of developing ACI. In the present haplotype-based case-control study, we investigated whether polymorphisms of the PTEN gene were associated with ACI in a Han Chinese population. Using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), we genotyped 300 patients with ACI and 204 matched healthy controls for five single nuclear polymorphisms (SNP) of the PTEN gene (rs2299939, rs17431184, rs555895, rs12357281 and rs2673836). Linkage disequilibrium and haplotype construction were analyzed using SHEsis software. We found that the rs2299939 PTEN intronic polymorphism was significantly associated with a risk of ACI in our Han Chinese population. The rs555895 and rs17431184C/T variants were not associated with risk of ACI. Two other polymorphisms were not detected in any subject in this study. The rs2299939C/rs17431184T/rs555895T PTEN haplotype was also significantly associated with risk of ACI. Our study provides the first evidence of an association between a PTEN intronic variant and the risk of ACI. It also provides new a new line of evidence for the critical role of PTEN in the development of stroke.

Fibrinogen polymorphisms associated with sporadic cerebral hemorrhage in a Chinese population

Fibrinogen plays an important role in the intrinsic and extrinsic pathways of blood coagulation. This study investigated the association between common variants in the fibrinogen gene and the risk of developing sporadic cerebral hemorrhage (CH). We performed genotyping analyses for three single nucleotide polymorphisms (SNP) in the fibrinogen gene in a case-controlled study involving 195 patients with CH and 116 control participants; both groups were of southern Han-Chinese origin. Logistic regression analysis indicated that haplotypes ATA (rs1800790+rs1800787+rs6050), AA (rs1800790+rs6050) and TA (rs1800787+rs6050) could nearly double the risk of sporadic CH (odds ratio [OR]=1.738, 95% confidence interval [CI]: 1.103-2.740, p=0.017; adjusted OR=1.762, 95% CI: 1.042-2.982, p=0.035), although the three SNP were not associated with sporadic CH when analyzed separately. These findings indicate that rs1800790, rs1800787 and rs6050 polymorphisms may contribute to the etiology of sporadic CH in the Chinese population.

Absence of association between atherosclerotic cerebral infarction and TNFSF4/TNFRSF4 single nucleotide polymorphisms rs1234313, rs1234314 and rs17568 in a Chinese population

Objective To clarify the association between atherosclerotic cerebral infarction (ACI) and the single nucleotide polymorphisms (SNP) rs1234313 and rs1234314 (in TNFSF4) and rs17568 (in TNFRSF4). Methods Genomic DNA was extracted from peripheral blood of patients with ACI and healthy control subjects. The presence of carotid plaque was determined. Rs1234313, rs1234314 and rs17568 were characterized via SNP genotyping assay and verified by DNA sequencing. Results Genotype distributions were in Hardy–Weinberg equilibrium. There were no significant differences in the allele and genotype distributions of rs1234313, rs1234314 and rs17568 between patients with ACI (n = 450) and healthy control subjects (n = 378), or between patients with ACI and carotid plaque (n = 342) and controls. Conclusions There were no significant associations between rs1234313, rs1234314 and rs17568 and ACI risk in a Han Chinese population.