Association Between Neurotensin Receptor 1 Gene Polymorphisms and Alcohol Dependence in a Male Han Chinese Population

Neurotensin (NT) is a 13-amino acid multifunctional neuropeptide. Previous studies have demonstrated the roles of NT and its high-affinity receptor 1 (NTR1) in genetically mediated differential sensitivities to alcohol. However, no studies have investigated the association between NTR1 gene single-nucleotide polymorphisms (SNPs) and alcohol dependence (AD). We therefore examined this link. We genotyped three SNPs (rs6090453C/G, rs6011914C/G, and rs2427422A/G) of NTR1 gene in 127 AD patients and 131 healthy controls drawn from Han Chinese males. Allele and genotype frequencies were compared, and linkage disequilibrium and haplotype analysis were performed. For rs6011914C/G, the frequencies of GG genotypes in AD patients showed an increased trend compared with controls (p?=?0.057), and the ratio of GG/(CG?+?CC) for dominant model in AD patients was significantly higher (p?=?0.024). For rs2427422A/G, both the frequencies of G alleles and GG genotypes and the ratio of GG/(AG?+?AA) for dominant model in AD patients were significantly higher compared with controls (p?=?0.003, 0.006, 0.002, respectively). There was no significant difference in the frequencies of alleles, genotypes, and dominant or recessive model for rs6090453C/G (all p?>?0.05). There were three pairs of SNP linkage disequilibriums, and the haplotype frequencies differed significantly between patients and controls for the CCA (p?=?0.005, less frequent in the patients) and CCG (p?=?0.002, more frequent in the patients) haplotypes. The current study supported an association between NTR1 gene variants and AD in the Han Chinese population.     

Influence of the 4600A/G and 4678G/C polymorphisms in the endothelial protein C receptor (EPCR) gene on the risk of venous thromboembolism in carriers of factor V Leiden

Two polymorphisms in the endothelial protein C receptor (EPCR) gene, 4600A/G and 4678G/C, have been reported to influence the risk of venous thromboembolism (VTE). The objective of this study was to assess whether these polymorphisms modify the risk of VTE in carriers of factor V (FV) Leiden. We genotyped 295 carriers of FV Leiden for these polymorphisms: 100 unrelated patients with a history of VTE (propositi) and 195 relatives (14 of them symptomatic) of 81 of the propositi. Spontaneous VTE events occurred in 71% of propositi carrying the 4678GG genotype, 65% carrying the GC, and 43% with the CC genotype. The mean age at the first onset was significantly higher in propositi carrying the 4678CC than in those with the GC or GG genotype (p = 0.046). Among the 276 carriers of FV Leiden from the 81 families studied, the 95 symptomatic members had similar 4600G allele and 4600AG genotype frequencies but significantly lower 4678C allele (p = 0.002) and 4678CC genotype (p = 0.004) frequencies than the 181 asymptomatic members. The probability of being free of thrombosis at age 40 was significantly higher in the 66 carriers of the 4678CC genotype (94%) than in the 138 carrying the GC (72%) or in the 72 with the 4678GG genotype (60%) (p < 0.001). Multivariate analysis showed that the 4678CC genotype reduced the risk of thrombosis in carriers of FV Leiden (OR = 0.31;95% CI = 0.16-0.83). The incidence of VTE was higher in the 195 relatives with FV Leiden than in the 133 without FV Leiden (OR = 4.7; CI = 1.3-7.2). These results show that carriers of FV Leiden with the 4678CC genotype have a significantly reduced risk of VTE compared with those carrying the 4678GG or GC genotype, probably due to the higherAPC levels previously observed in individuals carrying the 4678CC genotype.     

The (-174) G/C polymorphism in the interleukin-6 gene is associated with the severity of acute cerebrovascular events

BACKGROUND AND PURPOSE: Elevated plasma levels of interleukin-6 (IL-6) are associated with an increased risk and worse outcome of acute vascular events. A common G/C promoter polymorphism at nt (-174) of the IL-6 gene has been shown to affect basal IL-6 levels. Consequently, the IL-6 genotype may be associated with risk and outcome of ischemic stroke (IS). We investigated the statistical association between this polymorphism and cerebrovascular events, as well as the clinical outcome in patients with symptoms before the age of 60. METHODS: We examined 214 patients of 60 years or less with acute ischemic stroke or transient ischemic attack (TIA) and 214 age- and sex-matched healthy control subjects for the (-174) IL-6 G/C polymorphism by mutagenic separated polymerase chain reaction (MS PCR). Clinical severity of the vascular event was evaluated by validated scales at predefined points of time. RESULTS: In the total group of patients, the genotype and allele frequencies in the patient group (38% GG, 45% GC, 17% CC; allelic frequency: 60% G, 40% C) did not differ significantly from the control group. However, individuals homozygous for the (-174)G variant had significantly worse scores on the NIH Stroke Scale (NIHSS) already on admission and 1 week after the event. Also, patients with severe disability 1 week and 3 months after the event (Rankin Scale (RS) 4 or 5; NIH Stroke Scale> or =6) were significantly more often carriers of the GG genotype. In a multivariate analysis, the IL-6 (-174)GG genotype was significantly associated with severe disability after 1 week (RS 4-5; odds ratio (OR)=3.2, 95% CI: 1.5-6.6; p=0.002; NIHSS> or =6; OR=4.2, 95% CI: 1.6-11.1). CONCLUSIONS: The (-174)GG-genotype of the IL-6 gene is associated with severe stroke in young patients with acute cerebrovascular events. Further studies with larger patient groups are warranted to confirm these findings.     

Genetic variation in apolipoprotein D and Alzheimer’s disease

Apolipoprotein D (apoD) is a lipoprotein-associated glycoprotein, structurally unrelated to apoE, that transports small hydrophobic ligands including cholesterol and sterols. Levels are increased in the hippocampus and CSF of Alzheimer's disease (AD) patients. We tested whether variation in the APOD gene affects AD risk. Four single nucleotide polymorphisms (SNPs) were investigated (in map order): exon 2, 15T-->C encodes an amino acid substitution Phe-->Ser at codon 15; intron 2, -352G-->A; intron 3, +45C-->T; intron 4, +718C-->T, determined by SNaPshot assay. SNP frequencies for 394 eastern Finnish AD patients were compared with those found for 470 control subjects, dividing subjects also into early-onset AD (EOAD; < or = 65 years) and late-onset AD (LOAD; >65 years) groups. The -352G allele was associated with a significant 3-fold increase in the risk of EOAD (OR: 2.7; 95% CI: 1.1-6.5). The -352G containing haplotypes were more common for EOAD cases (TGCC: 0.48 vs 0.41; TGCT: 0.08 vs 0.01 (p = 0.002). In the Grade-of-membership analysis, APOD genotype frequencies at each SNP site and disease status were used to construct two latent groups: the affected group carried -352 as GG or GA and +45 CC, was often women and enriched in APOE epsilon4. Each method suggested that the -352G allele frequency is higher for EOAD in the eastern Finnish population.     

Impact of the PDE4D gene polymorphism and additional SNP–SNP and gene–smoking interaction on ischemic stroke risk in Chinese Han population

Aims: To investigate the association between phosphodiesterase 4D gene (PDE4D) gene single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) risk, and impact of additional SNP- SNP and gene- smoking interaction on IS risk in Chinese population.

Methods: A total of 1228 subjects (666 males, 562 females) were selected, including 610 IS patients and 618 control subjects. Logistic regression model was used to examine the association between SNPs in PDE4D gene and IS risk. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the SNP- SNP and gene- smoking interaction.

Results: IS risks were significantly higher in carriers of A allele of rs12188950 polymorphism than those with GG genotype (GA + AA vs. GG), adjusted OR (95%CI) = 1.61 (1.26–2.19), and also significantly higher in carriers of T allele of rs966221 polymorphism than those with CC (CT + TT vs. CC), adjusted OR (95%CI) = 1.82 (1.39–2.23). We found that there was a significant SNP- SNP interaction between rs966221 and rs12188950. Subjects with CT or TT of rs966221 and GA or AA of rs12188950 genotype have the highest IS risk, compared to subjects with CC of rs966221 and GG of rs12188950 genotype, OR (95%CI) was 3.52 (2.68–4.69). We also found a significant gene–environment interaction between rs966221 and smoking. Smokers with CT or TT of rs966221 genotype have the highest IS risk, compared to never smokers with CC of rs966221 genotype, OR (95%CI) was 3.97 (2.25–5.71).

Conclusions: Our results support an important association of rs966221 and rs12188950 minor allele and its interaction with increased risk of IS risk, and additional interaction between rs966221 and smoking.     

Cyclin-dependent kinase 5 is associated with risk for Alzheimer’s disease in a Dutch population-based study

Although the role of the Cdk5 protein in Alzheimer's disease (AD) is well recognized, there have been relatively few studies investigating genetic variants in the CDK5 gene in AD. In this study, we assessed the association between five previously described single nucleotide polymorphisms (SNPs) in the CDK5 gene and late onset AD by means of logistic regression and haplotype association analyses. Including all prevalent and incident AD cases, we found a significantly increased risk of AD for carriers of the GG genotype of SNP rs2069442 (OR = 1.79, 95 % CI 1.16-2.79, p = 0.001) in those without APOE*4. When limiting the analysis to incident cases without APOE*4, carriers of the GG genotype showed a 1.9-fold increased risk of AD (95 % CI 1.16-3.10, p = 0.003). Variations in the CDK5 gene can be described in 5 haplotype blocks. In our analysis, the haplotype tagged by the G allele of SNP rs2069442 was significantly associated with AD (p = 0.05). In conclusion, our study suggests that CDK5 may be associated with AD.     

Levels of the adipocyte-derived plasma protein, adiponectin, have a close relationship with atheroma

INTRODUCTION: Inflammation is a key process in atherosclerotic formation. Structural changes in the carotid arterial wall including detection of focal plaques are measured as the intima-media thickness (IMT) providing an index of atheroma. Coronary arterial plaques may be considered as vascular structural changes. Distensibility of the arteries can be assessed by functional changes in pulse wave velocity (PWV) providing an index of sclerosis. Adiponectin has potential antiatherosclerotic properties. We hypothesized that adiponectin was associated with atherosclerotic vascular changes involved in inflammation. MATERIALS AND METHODS: We enrolled 142 patients with coronary artery disease (CAD) and 108 control patients, matched for age, sex, and body mass index (BMI) with CAD patients. We investigated the relationship between adiponectin, C-reactive protein (CRP), and atherosclerotic vascular changes. RESULTS: CRP (p=0.0009), high-density lipoprotein cholesterol (HDL-C; p=0.02), and IMTmax (p=0.02) were determinants of adiponectin independent of glucose intolerance (p=0.0001), BMI (p=0.002), and CAD (p=0.03), all of which have been significantly associated with adiponectin (r=0.38). Adiponectin was not correlated with PWV. CRP, glucose intolerance, and HDL-C that correlated with adiponectin were inversely correlated with IMTmax and CAD. CRP was negatively correlated with HDL-C (r=-0.24, p=0.0002) and positively correlated with glucose intolerance (r=0.15, p=0.01). CONCLUSIONS: Adiponectin has a close relationship with CRP, IMTmax, CAD, HDL-C, and other established risk factors. CRP, glucose intolerance, and HDL-C are common mediators between adiponectin and atheromatous vascular changes, which are contrary to each other. The exacerbation of atherogenesis may be involved in a decrease of adiponectin through abnormal glyco- and lipid-metabolism by promoting inflammation.     

miRNA-146a基因多态性与婴儿痉挛的相关性

目的 探讨我国中部地区汉族人群中miR-146a基因SNP位点(rs2910164和rs57095329)多态性与婴儿痉挛易感性的关系.方法 采用病例对照研究方法,选取在武汉大学人民医院儿科188例婴儿痉挛患者为研究组,选取同期体检的健康儿童214名为对照组.利用PCR-RFLP方法检测rs2910164和rs57095329两个SNP位点的多态性分布.结果 miR-146a基因SNP位点rs57095329基因型(GG、AG、AA)频率分布和G等位基因频率与对照组比较,差异均有统计学意义(P＜0.05),但该位点基因频率与婴儿痉挛发作频率无相关性(P＞0.05).SNP位点rs2910164的基因型(CC、CG、GG)频率和等位基因C与对照组比较,差异均无统计学意义(P＞0.05).结论 位于miR-146a启动子区域的SNP位点rs57095329的多态性与婴儿痉挛的发病相关,但与其发作频率无相关性;而SNP位点(rs2910164)与婴儿痉挛的易感性不相关.     

Epistatic effects between variants of kappa-opioid receptor gene and A118G of mu-opioid receptor gene increase susceptibility to addiction in Indian population

Objective

Unequivocal evidence suggests contribution of κ-opioid receptor (KOR) in addiction to drugs of abuse. A study was undertaken to identify the single nucleotide polymorphisms (SNP) at selective areas of kappa opioid receptor 1 (OPRK1) gene in heroin as well as in alcohol addicts and to compare them with that in control population. The potential interaction of the identified KOR SNPs with A118G of μ opioid receptor was also investigated.

Methods

Two hundred control subjects, one hundred thirty heroin and one hundred ten alcohol addicts, all male and residing in Kolkata, a city in eastern India, volunteered for the study. Exons 3 and 4 of OPRK1 and the SNP, A118G of mu opioid receptor 1 (OPRM1) in the DNA samples were genotyped by sequencing and restriction fragment length polymorphism respectively. The SNPs identified in the population were analyzed by odds ratio and its corresponding 95% confidence interval was estimated using logistic regression models. SNP–SNP interactions were also investigated.

Results

Three SNPs of OPRK1, rs16918875, rs702764 and rs963549, were identified in the population, none of which showed significant association with addiction. On the other hand, significant association was observed for A118G with heroin addiction (χ² = 7.268, P = 0.0264) as well as with alcoholic addition (χ² = 6.626, P = 0.0364). A potential SNP–SNP interaction showed that the odds of being addicted was 2.51 fold in heroin subjects [CI (95%) = 1.1524 to 5.4947, P = 0.0206] and 2.31 fold in alcoholics [CI (95%) = 1.025 to 5.24, P = 0.0433] with the OPRK1 (rs16918875) and A118G risk alleles than without either. A significant interaction was also identified between GG/AG of A118G and GG of rs702764 [O.R (95%) = 2.04 (1.279 to 3.287), P = 0.0029] in case of opioid population.

Conclusion

Our study suggests that set associations of polymorphisms may be important in determining the risk profile for complex diseases such as addiction.     

The role of fibrinogen plasma levels, the -455G>A fibrinogen and the factor XIII A subunit (FXIII-A) Val34Leu polymorphism in cancer-associated venous thrombosis

Venous thromboembolism (VTE) is a life-threatening complication in cancer patients. Identification of risk factors has been in focus in the past years. Functional single nucleotide polymorphisms (SNP) of coagulation factors known to influence the concentration or function may be considered to influence the risk of VTE in cancer patients. We evaluated the influence of fibrinogen plasma levels, the -455G>A SNP in the fibrinogen beta gene and the Val34Leu (163G>T) SNP in the factor XIII A-subunit (FXIII-A) gene on the risk of VTE. In 1,079 tumour patients recruited for the prospective Vienna Cancer and Thrombosis Study (CATS) fibrinogen levels were determined by the Clauss method. The FXIII-A Val34Leu and the fibrinogen -455G>A SNPs were tested by allele-specific PCR. The median follow-up time was 604 days, 83 thrombotic events occurred. The median fibrinogen level was 381 mg/dl (25th-75th percentile: 312 to 467). In a multivariable Cox model adjusted to chemotherapy, surgery, radiotherapy, age and sex, neither the fibrinogen concentration (hazard ratio [HR] =1.05, confidence interval [CI] 0.839-1.310 p=0.68), nor the -455G>A SNP (HR=0.77, 95%CI 0.491-1.197; p=0.24), nor the Val34Leu SNP (HR=0.99, 95%CI 0.646-1.542 p=0.99) were associated with occurrence of VTE. The fibrinogen concentration was not significantly different among the fibrinogen -455G or A genotype carriers (p = 0.33). Disseminated intravascular coagulation was observed in only five patients, none of these developed VTE. In conclusion, fibrinogen plasma levels, the fibrinogen -455G>A and the FXIII-A Val34Leu polymorphisms were not associated with VTE in our study.     

Polymorphisms in the promoter region of the alpha1A-adrenoceptor gene are associated with schizophrenia/schizoaffective disorder in a Spanish isolate population.

BACKGROUND: Animal models have implicated the alpha(1)-adrenergic subtypes in cognitive functions relevant to schizophrenia, but no consensus exists with regard to the status of noradrenergic receptor populations in psychiatric patients. We focused on one alpha(1)-adrenergic subtype, the alpha(1A)-adrenergic receptor, and proposed that genetic variants within the regulatory region of this gene (ADRA1A) alter the expression of this receptor, influencing susceptibility toward schizophrenia. METHODS: This study examined this proposal by testing the hypothesis that single nucleotide polymorphisms (SNPs) in the promoter region of the alpha(1A)-adrenergic gene were associated with schizophrenia by performing case-control association analysis on SNPs found in a 5' upstream region, which included the putative promoter region and 5' untranslated region. Our sample consisted of 103 schizophrenia and 14 schizoaffective disorder patients and 176 control subjects. All recruits were from a Spanish population isolate of Basque origin that is characterized by low heterogeneity, which was selected with the intent that it might facilitate the identification of disease-related polymorphisms. RESULTS: A total of eight SNPs (-9625 G/A, -7255 A/G, -6274 C/T, -4884 A/G, -4155 C/G, -2760 A/C, -1873 G/A, and -563 C/T) were confirmed at a rare allele frequency of >5%. Association with schizophrenia and schizoaffective disorder was found for the -563 C/T SNP (p = .0005 for allele and p = .007 for genotype, Bonferroni corrected) and -9625 G/A SNP (p = .02 for allele and p = .03 for genotype, Bonferroni corrected). Significant differences in the 54 haplotypes formed by these eight SNPs were also found between patients and control subjects (p = .008, Bonferroni corrected). CONCLUSIONS: Because of the strength of these results and the location of these SNPs in the regulatory region of this gene, functional studies investigating the possible influence of these SNPs on receptor expression levels in schizophrenia are warranted.     

Fibrinolytic proteins and progression of coronary artery disease in relation to gemfibrozil therapy

Impaired fibrinolytic function, mainly due to increased plasma plasminogen activator inhibitor-1 (PAI-1) activity, is common in patients with manifest coronary artery disease (CAD) and a predictor of recurrent cardiovascular events. We investigated the relationships of plasma tissue-type plasminogen activator (tPA) and PAI-1 antigen levels, plasma PAI-1 activity and PAI 4/5-guanosine (4G/5G) genotype to CAD progression in 203 middle-aged men participating in the Lopid Coronary Angiography Trial (LOCAT). A higher tPA antigen concentration, whether baseline or on-trial, was associated with a more severe global angiographic response (p < 0.05), an association mainly accounted for by progression of diffuse lesions in graft-affected segments (change in per-patient means of average diameters of segments haemodynamically related to bypass grafts). Plasma PAI-1 activity and mass concentration and 4G/5G PAI-1 genotype were unrelated to angiographic outcome measurements. tPA and PAI-1 antigen increased significantly in the gemfibrozil group (+11.3% and + 16.4%, respectively, p < 0.001), whereas there was no treatment effect on PAI-1 activity (median change 0.0%). It is concluded that fibrinolytic function does not substantially influence progression of CAD as assessed by angiography in middle-aged men. Furthermore, pronounced long-term lowering of serum triglycerides by gemfibrozil treatment does not significantly affect the plasma PAI-1 activity level but increases the plasma tPA and PAI-1 antigen concentrations.     

脂联素基因多态性在抗精神病药对糖脂代谢影响中的意义

目的了解精神分裂症患者的脂联素基因外显子2T45G多态性,并探讨其与应用非典型抗精神病药治疗相关的肥胖以及糖代谢的关系。方法入组患者组125例为应用非典型抗精神病药的精神分裂症患者,正常对照组59例。提取两组基因组DNA,采用聚合酶链式反应-限制片段长度多态性技术,检测脂联素（Adi）基因外显子2T45G多态性和等位基因分布频率。采用免疫酶吸附（ELISA）法分别测定两组血脂,空腹血糖、胰岛素水平计算胰岛素抵抗指数（HOMA-IR）,测量身高、体质量,计算体质量指数（BMI）,并将两组对照比较。结果使用抗精神病药的患者与正常对照组之间脂联素基因型分布及等位基因频率均差异无显著性（χ^2=0．723,0．257;P=0．697,0．613）。携带TG／GG基因型患者的BMI显著高于携带TT型患者（23．53±2．77vs22．37±3．11,P〈0．05）,且携带TG／GG型患者低密度脂蛋白（LDL—C）水平显著高于携带,TT型患者（2．67±0．85vs2．28±1．15,P〈0．05）。携带TT和TG／GG型基因的患者之间的胰岛素抵抗及血脂其他各项差异均无显著性（P〉0．05）;多元线性回归分析示Adi基因外显子2T45G多态性与HOMA—IR并不相关。结论Adi基因外显子2T45G多态性与非典型抗精神病药物治疗相关的脂代谢异常相关,但不是影响血糖代谢障碍的基因危险因子。     

Association between adiponectin gene polymorphisms and coronary artery disease across different populations

Objective

Many studies have suggested that adiponectin gene might be involved in the development of coronary artery disease (CAD). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to assess the associations of + 45T/G, + 276G/T and − 11377C/G polymorphisms in adiponectin gene with CAD susceptibility.

Methods

Published literature from PubMed and EMBASE databases were searched. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated using fixed- or random-effects model.

Results

Sixteen studies (4394 cases / 8187 controls) for + 45T/G polymorphism, fifteen studies (3569 cases / 7463 controls) for + 276G/T polymorphism, and thirteen studies (3531 cases / 7072 controls) for − 11377C/G polymorphism were included in the meta-analysis. The overall results showed that there was a statistically significant association between − 11377C/G polymorphism and CAD (G vs. C: OR = 1.15, 95%CI 1.07-1.24).Similar results were observed among European (G vs. C: OR = 1.11, 95%CI 1.02-1.20) and East Asian populations (G vs. C: OR = 1.27, 95%CI 1.11-1.45). However, no significant association was found for + 45T/G or + 276G/T polymorphism with CAD susceptibility.

Conclusions

The meta-analysis indicated the significant association of − 11377C/G polymorphism, but not + 45T/G or + 276G/T polymorphism, with CAD susceptibility. However, large-scale studies with the consideration of gene-gene and gene-environment interactions should be conducted to investigate the associations in future.     

广西百色地区壮族男性人群骨密度与脂联素基因单核苷酸多态性的关系***

背景：脂联素可在骨代谢中发挥重要作用。 目的：观察脂联素基因单核苷酸多态性与广西百色地区壮族男性骨密度的关系。 方法：选取广西百色地区壮族男性跟骨骨量减少患者,采用单碱基延伸的单核苷酸多态性分型技术对广西百色地区302例壮族男性的脂联素基因的5个单核苷酸多态性位点(rs1063539、rs12495941、rs266729和rs3774261)进行了基因分型。 结果与结论：以5个多态性位点作为自变量的多元 Logistic回归检测结果显示,仅rs3774261多态性与跟骨超声振幅衰减显著相关(OR=1.948,95%CI：1.184~3.203,P < 0.01),并独立于骨量减少的传统危险因素。对基因型进行纯合子与杂合子合并后的协方差分析显示,仅rs3774261的AG+GG与AA基因型的跟骨超声振幅衰减值差异有显著性意义(P < 0.05),AG+GG型对骨密度具有一定的保护作用,AA型是骨密度降低的危险因素。结果证实,脂联素基因第2内含子rs3774261位点多态性与中国百色地区壮族男性骨密度有一定关联。     

Carotid dissection with and without ischemic events: local symptoms and cerebral artery findings

OBJECTIVE: To study whether spontaneous dissections of the cervical internal carotid artery dissection (ICAD) with and without ischemia of the brain or retina differ in the prevalence of vascular risk factors, local neurologic signs and symptoms, and stenoses and occlusions of the cerebral arteries. METHODS: The authors prospectively studied 181 consecutive patients with 200 ICAD. Diagnosis was based on ultrasonography and MRI or catheter angiography. Vascular risk factors, presenting local (headache, neck pain, Horner syndrome, pulsatile tinnitus, cranial nerve palsy on the side of the ICAD) and ischemic signs and symptoms, and ultrasonographic findings in the carotid and basal cerebral arteries were evaluated. RESULTS: ICAD with ischemic events (n = 145) had a higher prevalence of hypercholesterolemia (p < 0.05), >80% stenoses and occlusions of the ICA (p < 0.0001), and intracranial obstructions (p < 0.001). ICAD without ischemic events (n = 55) had a higher prevalence of Horner syndrome (p < 0.001), cranial nerve palsy (p < 0.01), and normal ICA findings (p < 0.0001). CONCLUSIONS: These data suggest that ICAD causing high-grade stenosis and occlusion are more likely to lead to intracranial obstructions and cerebral or retinal ischemic events. Conversely, ICAD without luminal narrowing cause more local signs and symptoms.     

Suicide,stress and serotonin receptor 1A promoter polymorphism -1019C>G in Slovenian suicide victims

Implication of serotonergic system in suicide and suicide attempts has been discussed for several years. One of the most abundant serotonin receptors in the mammalian brain is the receptor 1A (5-HT1A); studies of its polymorphisms and suicide have provided very inconsistent results so far. The suggestion that the G allele depresses HTR1A autoreceptor expression, and therefore reduces serotonergic neurotransmission that might predispose to depression and suicide, made the promoter polymorphism -1019C>G a very promising candidate gene. In our study we analyzed promoter polymorphism -1019C>G on 323 suicide victims and 190 controls (all of Slovenian origin), taking into account sex, suicide method, and in case of suicide victims also stressful life events. Differences in the distributions of genotype and allele frequencies were not statistically significant between suicide victims and control group, and the same was found for distributions according to sex and suicide method. For 62 suicide victims information about stressful life events in the month prior to the suicide and in childhood was provided. For analysis we combined CG/GG genotypes and compared them to the CC genotype. More stressful life events in the month prior to the suicide were reported for the subgroup with CC genotype (mean number of events = 2.53; SD = 1.50) in comparison to subgroup with CG/GG genotypes (mean number of events = 1.58; SD = 1.32; P < 0.05). However, subgroups of suicide victims with CC or CG/GG genotypes did not differ regarding numbers of reported stressful life events in childhood (P > 0.05). Our study provides no evidence for the implication of HTR1A promoter polymorphism in suicide in general, but it suggests further studies that would take into account the interconnected network of suicide completion, genetic background and stress, beside other risk factors.     

Risk of cerebral venous thrombosis and novel gene polymorphisms of the coagulation and fibrinolytic systems

BACKGROUND AND PURPOSE: Genetic thrombophilic conditions such as those associated with Factor V Leiden (FVL) and the prothrombin mutant (PT G20210A) have been identified as risk factors for cerebral venous thrombosis (CVT). Recently, a single nucleotide polymorphism (SNP) of the thrombin activatable fibrinolysis inhibitor (TAFI G-438A) has been shown to be associated with lower TAFI levels and to decrease the risk for peripheral venous thrombosis. Furthermore, a protective role in juvenile stroke was shown for a SNP of the vitamin K dependent protein Z (PZ Intron F G79A) which is linked with low PZ levels. PATIENTS AND METHODS: In 77 consecutive patients with CVT and in 203 randomly selected population controls from the same region of Southern Germany, we investigated the following functional SNPs using PCR and restriction fragment analysis techniques: TAFI G-438A, PZ Intron F G79A, FVL and PT G20210A. RESULTS: The prevalence of FVL tended to be higher (OR 2.08, 95 % CI 0.91-4.75, p = 0.06) and that of PT G20210A (OR 4.57, 95 % CI 1.45-14.44, p = 0.007) was significantly higher in patients with CVT than in controls. The A-allele frequency of the TAFI G-438A polymorphism did not significantly differ between patients (21.3 %) and controls (26.9%; OR 0.71, 95 % CI 0.45-1.12; p = 0.17). For the PZ G79A SNP, the frequency of the A-allele was 19.5% in CVT and 24.6% in controls (OR 0.77, 95 % CI 0.49-1.21; p = 0.31). CONCLUSIONS: In this large series of CVT patients, a positive association with established thrombophilic risk factors FVL and especially the PT G20210A mutation was confirmed. In contrast, our study found no significant association of CVT with SNPs of the TAFI and the PZ genes. Other than testing for FVL and the PT G20210A mutation, exploration of these potential thrombophilic variants seems to be of limited value in the investigation of CVT.     

聚集素基因多态性与脑卒中后血管性痴呆的相关性分析

目的 探讨聚集素基因多态性与脑卒中后血管性痴呆的关系。方法 选取2019年12月-2020年12月本院收治的88例脑卒中后血管性痴呆患者作为观察组,并选取同期体检健康的60例健康者作为对照组,采用竞争性等位基因特异性聚合酶链反应(Kompetitive allele specific polymerase chain reaction,KASP)基因分型检测技术和基因测序法测定聚集素基因多态性(rs11136000和rs9331888位点基因亚型和等位基因分布频率),分析聚集素基因多态性与脑卒中后血管性痴呆的相关性。结果 2组基因分布符合哈代-温伯格(Hardy-Weinberg)平衡(F值分别为0.439和0.546,P>0.05),2组基因型分布频率达到基因遗传平衡标准,可体现人群基因分布情况,样本具有代表性,且观察组聚集素基因rs11136000位点TT基因型(1.14%)、TG基因型(32.95%)和T等位基因(43.18%)分布频率显著低于对照组的8.33%、50.00%、60.00%,而GG基因型(65.91%)和G等位基因(97.73%)分布频率显著显著高于对照组的40.00%和88.33%(P<0.05)。观察组聚集素基因rs9331888位点CC,CG,GG基因型和C,G等位基因分布频率与健康组比较无明显差异(P>0.05)。观察组合并糖尿病史和高脂血症史的比例和总胆固醇水平显著高于对照组,脑卒中后血管性痴呆与糖尿病史、总胆固醇水平、高脂血症史密切相关(P<0.05),与受教育年限、高血压病史、冠心病史、甘油三酯水平、婚姻状况、心律失常史、心肌梗死史、贫血史等因素无关(P>0.05)。对有统计学意义的相关因素进行多因素Logistic 回归分析显示,糖尿病史(OR=1.677,95%CI=1.083～2.596)、总胆固醇水平(OR=1.587,95%CI=1.041～2.419)、携带GG基因型(OR=2.812,95%CI=1.341～5.900)、携带G等位基因(OR=2.863,95%CI=1.411～5.810)是脑卒中后血管性痴呆发生的独立危险因素(OR>1,P<0.05)。结论 聚集素基因rs11136000位点GG基因型、G等位基因分布频率与脑卒中后血管性痴呆发生相关,在脑卒中后血管性痴呆患者体内聚集素基因rs11136000位点GG基因型和G等位基因分布频率较高,可为临床脑卒中后血管性痴呆发生的早期识别提供参考依据。     

脂联素基因单核苷酸多态rs266729、 rs2241766、rs822396与老年缺血性 脑血管病亚型相关性研究

目的 探讨中国北方青岛地区汉族人群脂联素（adiponectin,ADIPOQ）基因多态性与老年缺血性脑血
管病发病的相关性。
方法 入组年龄大于60岁的老年缺血性脑血管病患者,按急性卒中治疗低分子肝素试验（Trial
of Org 10172 in Acute Stroke Treatment,TOAST）分型,选取大动脉粥样硬化性（large artery
atherosclerosis,LAA）和小动脉闭塞性（small artery occlusion,SAO）两种亚型患者,其中LAA 144例,
SAO 221例;402例同期查体者进行病例对照研究。对比两组的ADIPOQ基因多态性。
结果 rs266729（-11377C/G）的基因型分布在LAA组、SAO组与对照组3组中有显著差异（P =0.036）。
3组中两两比较显示,SAO组中rs266729（-11377C/G）GG基因型分布显著高于对照组（P =0.009）;在
隐性［P =0.004,比值比（odds ratio,OR）=2.478,95%可信区间（confidence interval,CI）=1.31～4.70］、
累加模式（P =0.003,OR 2.680,95%CI 1.39～5.15）下,rs266729（-11377C/G）基因型分布在SAO组与
对照组中也有显著差异,G 等位基因能增加SAO型缺血性脑血管病的风险,但在显性模式下差异无显
著性。rs822396（-3964A/G）、rs2241766（-45T/G）的基因型分布在LAA组、SAO组与对照组3组中均
无显著差异。
结论 rs266729（-11377C/G）G 等位基因与老年缺血性脑血管病发病相关,其G 等位基因变异可增
加老年患者SAO型缺血性脑血管病的风险。