Effects of major adipokines and the −420 C > G resistin gene polymorphism on the long-term outcome of patients with acute ischemic stroke

Abstract

Aim: The association between adiponectin, leptin, and resistin and the long-term outcome of ischemic stroke are controversial. We aimed to evaluate this relationship.

Methods: We prospectively studied 83 patients consecutively hospitalized for acute ischemic stroke (38.6% males, age 79.7?±?6.3?years). Serum adiponectin, leptin, and resistin levels and the ?420C?>?G polymorphism of the resistin gene were determined at admission. Stroke severity at admission was evaluated with the National Institutes of Health Stroke Scale (NIHSS). One year after discharge, functional status, incidence of cardiovascular events and all-cause mortality were recorded. Functional status was evaluated with the modified Rankin scale (mRS).

Results: Patients with the G allele had lower mRS (p?<?.05) and patients with adverse outcome had higher serum resistin levels (p?<?.05). The only independent predictor of adverse outcome was mRS at discharge (risk ratio (RR) 2.78, 95% confidence interval (CI) 1.54–5.00; p?<?.001). Higher adiponectin levels were an independent predictor of cardiovascular morbidity (RR 1.07, 95% CI 1.01–1.14; p?<?.05). Patients who died had higher serum adiponectin levels than those who survived (p?<?.05). The only independent predictor of all-cause mortality was NIHSS at admission (RR 1.19, 95% CI 1.04–1.35; p?<?.01).

Conclusions: In patients with acute ischemic stroke, the G allele of the ?420C?>?G polymorphism of the resistin gene promoter is more frequent in those with a more favorable functional outcome at one year after discharge. Patients with higher serum resistin levels appear to have worse long-term functional outcome, while higher serum adiponectin levels are associated with higher incidence of cardiovascular events.     

Association analysis of the −308G > A promoter polymorphism of the tumor necrosis factor alpha (TNF-α) gene in Japanese patients with schizophrenia

Summary. Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (–308G > A) of the gene encoding tumor necrosis factor alpha (TNF-), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the –308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the –308G > A polymorphism of the TNF- gene.     

Association of monocyte chemoattractant protein-1 −2518A>G polymorphism with occurrence, severity, and outcome in ischemic stroke

Monocyte chemoattractant protein-1 (MCP-1) is implicated in promoting atherosclerotic diseases, including stroke. Therefore, several studies have investigated the association between variants of the MCP-1 gene and risk of atherosclerotic diseases. We sought to determine the occurrence of MCP-1 ?2518A>G polymorphism in patients with ischemic stroke (IS), and studied its association with the severity of disease and functional outcome after an acute IS. One hundred and forty-five consecutive patients with first ever IS and 145 age- and sex-matched control subjects were recruited. Stroke severity and functional outcome were assessed on admission and at one month post-stroke, respectively. Genotyping for the MCP-1 ?2518A>G polymorphism was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significant difference in the frequency of MCP-1 ?2518A>G genotypes between IS patients and controls was found, with OR = 0.69 (95 % CI 0.46–1.04, P = 0.08). Moreover, carriage of the G allele was not associated with stroke severity (Scandinavian stroke scale score 33.1 vs. 32.5, respectively, P = 0.71), or poor outcome at 1 month post-stroke (63.9 vs. 59.7 %, respectively, P = 0.61). In conclusion, we were unable to demonstrate a significant association of the MCP-1 ?2518A>G gene polymorphism with IS occurrence, severity or functional outcome in a Caucasian population. However, larger studies are necessary to fully elucidate the role of this polymorphism in IS.     

The β-fibrinogen –455G/A gene polymorphism and the risk of ischaemic stroke in a Polish population

Background and purposeIschaemic stroke is considered to be multifactorial and interactions between environmental and genetic factors play an important role. Although vascular risk factors are well known, the genetic ones are still undiscovered. In the present study, we assessed the significance of the β-fibrinogen –455G/A gene polymorphism and the risk of ischaemic stroke in a Polish population.Material and methods426 ischaemic stroke patients classified according to stroke aetiologies (small vessel disease, large vessel disease or cardioembolic stroke) and 234 controls were included in the study. The association of the β-fibrinogen genotypes with ischaemic stroke was tested using logistic regression analysis under dominant, recessive or additive models of inheritance.ResultsThe allele and genotype distributions of the β-fibrinogen –455G/A gene polymorphism did not differ significantly between patients and controls (patients: G – 75%, GG – 56.6%, GA – 36.8%, AA – 6.6%; controls: G – 73.7%, GG – 57.3%, GA – 32.9%, AA – 9.8%; p > 0.05, χ²). In addition, logistic regression analysis adjusted for the known risk factors, i.e. hypertension, ischaemic heart disease, myocardial infarction, hypercholesterolaemia, diabetes mellitus and smoking, did not show a role of the studied polymorphism in ischaemic stroke.ConclusionsThe β-fibrinogen –455G/A gene polymorphism is not a risk factor for ischaemic stroke in a Polish population.     

Lack of association between monocyte protein-1 (MCP-1) –2518 A > G chemoattractant and C–C chemokine receptor 2 (CCR2) Val64Ile polymorphisms and multiple sclerosis in a Tunisian population

Chemokines and their receptors are known to mediate inflammation and tissue damage in autoimmune disorders such as multiple sclerosis (MS). Multiple sclerosis is an inflammatory disease of the central nervous system, characterized by myelin damage and neurological complications. Monocyte chemoattractant protein-1 (MCP-1) interacts with the C–C chemokine receptor 2 (CCR2) and plays a role in the migration of leukocytes into the central nervous system, thus contributing to the T cell-mediated pathogenesis of MS. Genomic DNA obtained from 58 MS patients and 72 healthy controls was tested for the MCP-1 –2518 A > G and CCR2 Val64Ile polymorphisms using polymerase chain reaction–restriction fragment length polymorphism analysis. Neither the MCP-1 –2518G (p = 0.43) nor the CCR2 64Ile (p = 0.52) variant contributed to the risk of MS in Tunisians.     

Promoter polymorphism (–491A/T) in the APOE gene of Finnish Alzheimer’s disease patients and control individuals

Apolipoprotein E (APOE) ɛ4 allele is a major risk factor for the development of Alzheimer’s disease (AD). It has been suggested that the quantitative expression of APOE alleles results from mutations in the promoter region of this gene. We studied the –491A/T promoter polymorphism and whether it is dependent on the APOE ɛ4 allele in clinic-based AD (n = 106) and community-based control (n = 123) samples. The –491A/T and APOE polymorphisms were analyzed using the polymerase chain reaction method and restriction fragment length polymorphism analysis. The APOE ɛ4 allele was strongly associated with AD when compared with controls, P < 0.001 (odds ratio 5.85, 95% CI 3.29– 10.41). The genotype distribution of the –491A/T polymorphism did not significantly differ between the study groups (P = 0.063), and the –491A allele was not associated with any significant risk in the AD group when compared to controls (odds ratio 1.82, 95% CI 0.95–3.49). However, haplotype estimation analysis indicated linkage disequilibrium between APOE –491A/T polymorphism and the APOE ɛ4 allele. Our findings confirm APOE polymorphism still to be the most efficient predictor of risk in AD. Received: 2 November 1998 Received in revised form: 28 January 1999 Accepted: 5 February 1999     

The association between personality,pain threshold and a single nucleotide polymorphism (rs3813034) in the 3′-untranslated region of the serotonin transporter gene (SLC6A4)

In 181 healthy Japanese volunteers we examined the relationship between personality, sensitivity to pain and a single nucleotide polymorphism (rs3813034) in the 3′ untranslated region (3′ UTR) of the serotonin transporter (5-HTT) gene (SLC6A4). Pain sensitivity was assessed by using cold and pressure thresholds. Personality was assessed by the Temperament and Character Inventory (TCI). Males without the T allele (G/G) showed a significantly higher spiritual acceptance (ST3) score than those who had the T allele (T/T and T/G). Females with the T allele (T/T and T/G) showed significantly higher transpersonal identification (ST2) and self-transcendence (ST) scores than those without the T allele (G/G). As for pain sensitivity and its relationship with TCI, we found a low negative correlation between cold water stimulation, disorderliness (NS4) and novelty seeking (NS) in males, whereas in females we found a low positive correlation between cold water stimulation, self-acceptance (SD4) and pure-hearted principles (C5), as well as pressure stimulation and SD4. It is possible that the 5-HTT 3′ UTR gene polymorphism affects the character dimensions of Cloniger’s theory, and that there might be a low correlation between pain and a part of the personality.     

Lack of association between the brain-derived neurotrophin factor (C-270T) polymorphism and late-onset Alzheimer’s disease (LOAD) in Brazilian patients

After the identification of the apolipoprotein E gene isoform (APOE-ε4) as a risk factor for late-onset Alzheimer’s disease (LOAD), the search for other polymorphisms associated with AD has been undertaken by many groups of investigators around the world. These studies have shown controversial results in many populations. More recently, a single nucleotide polymorphism in the promoter region of the brain-derived neurotrophin factor (BDNF) was found to be a risk factor for AD in two independent population studies. Here we report the analysis of this polymorphism in a group of 188 LOAD Brazilian patients compared to matched normal controls. A strong association between the APOE-ε4 polymorphism and LOAD was observed, but there was no significant association between this BNDF polymorphism and affected patients. The possibility that other polymorphisms or mutations in this gene play a role in the development of AD cannot be ruled out. However, the results of the present study suggest that in opposition to the two reported studies, this polymorphism does not seem to be implicated in LOAD Brazilian patients. It also shows the importance of replication studies in different populations, as susceptibility loci might differ in different ethnic groups; this will have important implications in future treatments with pharmacological agents.     

Risk factors and outcomes of postoperative stroke in surgical treatment for giant intracranial aneurysms

Background: Giant intracranial aneurysms (GIAs) are challenges for surgical treatment. Risk factors of postoperative stroke remain unclear. This study aims to investigate the predictors of postoperative stroke in GIAs and the impact of stroke on outcomes.Methods: We performed a retrospective medical record review of patients with GIAs who received microsurgery at our institution between 2011 and 2018. Multivariate logistic regression analyses were carried out to identify risk factors for postope...     

Prevalence of positive syphilis serology and meningovascular neurosyphilis in patients admitted with stroke and TIA from a culturally diverse population (2005–09)

The study aims were to determine the prevalence of positive syphilis serology and meningovascular neurosyphilis (NS) in patients admitted with transient ischaemic attack (TIA) and stroke to a tertiary hospital serving a culturally diverse community. A retrospective cohort analysis was conducted using routinely collected administrative data and medical records to identify patients admitted with TIA, stroke and other conditions, with positive syphilis serology, between 2005 and 2009. Direct medical record review confirmed diagnoses of meningovascular NS. Syphilis serology was requested in 27% (893/3270) of all patients with TIA and stroke (2005–09) of whom 4% (38/893) were positive. Thirty-seven patients with positive serology had clinical characteristics consistent with meningovascular NS. Their mean age was 72 ± 13 years; 65% were male and 68% had a recorded place of birth in South-East Asia or the Pacific Islands. One of 12 patients with suspected meningovascular NS with cerebrospinal fluid (CSF) analysis had a positive CSF Venereal Disease Research Laboratory (VDRL) test. Three patients (8%) met diagnostic criteria for “definite or probable” meningovascular NS. All three patients with a “definite or probable” meningovascular NS and 15 (44%) of the remainder who had positive serology without confirmation of NS were treated with intravenous or intramuscular penicillin. Lumbar puncture (LP) and penicillin were underutilised in patients with TIA and stroke with positive serology. In conclusion, syphilis testing should be considered part of the diagnostic work-up of TIA and stroke, particularly in ethnically diverse populations. In patients with TIA and stroke with positive syphilis serology, it would seem appropriate to further pursue diagnosis and treatment and in patients unable to undergo LP, empiric treatment for NS should be considered.     

No significant association between Catechol-O-methyl transferase (COMT) ?287A/G gene polymorphism and Tourette��s syndrome in family-based association study in Chinese Han population

To identify the association of Catechol-O-methyl transferase (COMT) -287A/G polymorphism with susceptibility to TS in Chinese Han population. We evaluated the genetic contribution of the COMT -287A/G polymorphism in 108 TS patients including all their parents in Chinese Han population using transmission disequilibrium test and haplotype relative risk design. Our results revealed that no significant association was found in COMT -287A/G genotypic and allelic frequencies with TS. Our results also suggested that there may be a lack of association between the TS and -287A/G polymorphism of COMT in Chinese Han population.     

Interleukin 6–174 G/C promoter and variable number of tandem repeats (VNTR) gene polymorphisms in sporadic Alzheimer's disease

Background

Previous studies examining the association between the interleukin 6 (IL-6)–174 C/G polymorphism and Alzheimer's disease (AD) have yielded conflicting results. Furthermore, the C allele of the IL-6 variable number of tandem repeats (VNTR) polymorphism was associated with a delayed onset and a decreased risk of AD.

Methods

A total sample of 149 AD patients, and 298 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were genotyped for the apolipoprotein E (APOE) polymorphism, the VNTR polymorphism in the 3' flanking region, and the -174G/C single-nucleotide polymorphism (SNP) in the promoter region of IL-6 gene on chromosome 7. Furthermore, we performed a haplotype analysis on these two polymorphisms on IL-6 locus.

Results

IL-6 VNTR and -174G/C allele and genotype frequencies were similar between AD patients and controls, also after stratification for late-onset (≥ 65 years) and early-onset (< 65 years) or APOE ε4 status. Furthermore, there was no evidence of linkage disequilibrium between the VNTR and -174G/C polymorphisms, not supporting a previous reported additive effect of both IL-6 polymorphisms on AD risk.

Conclusions

Our findings did not support a role of IL-6–174 G/C and IL-6 VNTR polymorphisms in the risk of sporadic AD in southern Italy, suggesting that these polymorphisms of IL-6 gene were at most weak genetic determinants of AD.     

Association between polymorphism in the promoter region of <Emphasis Type="Italic">Interleukin 6</Emphasis> (-174 G/C) and risk of Alzheimer’s disease: a meta-analysis

Studies of the relationship between Alzheimer’s disease (AD) and polymorphism in the promoter region of Interleukin 6 (IL-6) -174 G/C have reported inconsistent results. To assess the association between IL-6 -174 G/C promoter polymorphism and AD risk, a meta-analysis containing 3,101 AD cases and 3,860 controls from 18 case–control studies was performed. There were 16 studies involving Europeans and 2 studies involving non-Europeans. The combined results showed significant differences in recessive model [CC versus GC + GG, odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.54–0.90] and heterozygote comparison (CC versus GC, OR = 0.76, 95% CI = 0.60–0.96) on the basis of all studies. On subgroup analysis by ethnicity, similarly significant differences in recessive model (CC versus GC + GG) were found in both Europeans and non-Europeans, but significant difference in heterozygote comparison (CC versus GC) was found only in non-Europeans. In conclusion, there were statistically significant differences in genotype distribution of IL-6 -174 G/C between AD cases and controls in recessive model (CC versus GC + GG). Genotype CC of IL-6 -174 G/C could decrease the risk of AD. Further studies with large sample size, especially in subgroup analysis, should be done.     

Association studies of the adenosine A2a receptor (1976T > C) genetic polymorphism in Parkinson’s disease and schizophrenia

Summary. Given the implications with respect to the pathogenesis of dopaminergic dysfunction in schizophrenia and Parkinson’s disease (PD), as well as the reciprocal antagonistic interactions between adenosine A2a receptor (A2aAR) and the dopamine D2 receptors, A2aAR may be a candidate gene conferring susceptibility to PD or schizophrenia. In this study, we tested the hypothesis that the A2aAR 1976T > C genetic variant confers susceptibility to or is related to the onset age of schizophrenia or PD using a sample population consisting of 94 PD and 227 schizophrenic patients. We also tested whether the A2aAR 1976T > C relates to antipsychotic-induced tardive dyskinesia in the schizophrenic population. The results demonstrated that in comparing PD patients and controls the distribution of the A2aAR 1976T > C genotypes (P = 0.788) and alleles (P = 0.702) did not vary significantly. Furthermore, the PD onset age was not significantly different amongst the three A2aAR 1976T > C genotypic groups. In comparing schizophrenic patients and controls, the distribution of the A2aAR genotypes (P = 0.330) and alleles (P = 0.632) also did not differ significantly. The onset age of schizophrenia and tardive dyskinesia (evaluated with Abnormal Involuntary Movements Scale) were similar within the three A2aAR genotypic groups. Our findings suggest that it is unlikely that the A2aAR 1976T > C polymorphism plays a major role in the pathogenesis of PD, schizophrenia, or antipsychotic-induced tardive dyskinesia in the Chinese population.     

Suicidal ideation and associated factors among students aged 13–15 years in Association of Southeast Asian Nations (ASEAN) member states, 2007–2013

Objective: The aim of this study was to assess suicidal ideation and associated factors in school-going adolescents in the Association of Southeast Asian Nations (ASEAN) member states.

Methods: The analysis included 30,284 school children aged 13–15 years from seven ASEAN countries that participated in the cross-sectional global school-based student health survey (GSHS) between 2007 and 2013.

Results: The overall prevalence of suicidal ideation in the past 12 months across seven ASEAN countries was 12.3%, significantly higher in girls (15.1%) than boys (9.3%). Among seven ASEAN countries with the highest prevalence of suicidal ideation was in the Philippines (17.0%) and Vietnam (16.9%) and the lowest in Myanmar (1.1%) and Indonesia (4.2%). In multivariable logistic regression analysis, female gender, older age (14 or 15 years), living in a lower middle income country, having no friends, loneliness, bullying victimisation, having been in a physical fight in the past 12 months, lack of parental or guardian support, tobacco use and having a history of ever got drunk were associated with suicidal ideation.

Conclusions: Different rates of suicidal ideation were observed in ASEAN member states. Several risk factors for suicidal ideation were identified which can help guide preventive efforts.     

A founder mutation in the GMPPB gene [c.1000G > A (p.Asp334Asn)] causes a mild form of limb-girdle muscular dystrophy/congenital myasthenic syndrome (LGMD/CMS) in South Indian patients

neurogenetics - Twelve patients from seven unrelated South Indian families with a limb-girdle muscular dystrophy-congenital myasthenic syndrome (LGMD/CMS) phenotype and recessive inheritance...