共查询到20条相似文献,搜索用时 31 毫秒
1.
Marianna Trebunova Eva Slaba Viera Habalova Zuzana Gdovinova 《Central European Journal of Biology》2008,3(1):49-54
Angiotensin-converting enzyme (ACE) has been reported to show altered activity in patients with neurological diseases. The
recent studies found that a 287 bp insertion/deletion (I/D) polymorphism of the ACE gene may be associated with susceptibility
to Alzheimer’s disease (AD) but the results have been heterogenous between studies in Europe. In the present study we examined
for the first time the association of ACE I/D polymorphism along with APOE genotype in 70 sporadic AD and 126 control subjects
in Slovak Caucasians (Central Europe). An increased risk for AD was observed in subjects with at least one APOE*E4 allele
(OR=3.99, 95% CI=1.97–8.08). No significant differences for the genotype distribution or the allele frequency were revealed
comparing controls and patients for ACE gene. Gene-gene interaction analysis showed increase of the risk to develop AD in
subjects carrying both the ACE DD genotype and the APOE*E4 allele (OR=10.32, 95% C.I. 2.67–39.81). 相似文献
2.
Jorge A. Serra Raúl O. Domínguez Enrique R. Marschoff Eduardo M. Guareschi Arturo L. Famulari Alberto Boveris 《Neurochemical research》2009,34(12):2122-2132
Markers of oxidative stress were measured in blood samples of 338 subjects (965 observations): Alzheimer’s, vascular dementia,
diabetes (type II) superimposed to dementias, Parkinson’s disease and controls. Patients showed increased thiobarbituric acid
reactive substances (+21%; P < 0.05), copper-zinc superoxide dismutase (+64%; P < 0.001) and decreased antioxidant capacity (−28%; P < 0.001); pairs of variables resulted linearly related across groups (P < 0.001). Catalase and glutathione peroxidase, involved in discrimination between diseases, resulted non-significant. When
diabetes is superimposed with dementias, changes resulted less marked but significant. Also, superoxide dismutase resulted
not linearly correlated with any other variable or age-related (pure Alzheimer’s peaks at 70 years, P < 0.001). Systemic oxidative stress was significantly associated (P ≪ 0.001) with all diseases indicating a disbalance in peripheral/adaptive responses to oxidative disorders through different
free radical metabolic pathways. While other changes—methionine cycle, insulin correlation—are also associated with dementias,
the responses presented here show a simple linear relation between prooxidants and antioxidant defenses. 相似文献
3.
Schizophrenia is a chronic and disabling disease of the brain. Schizophrenic patients have auditory hallucinations, delusions
and reduced social skills. Recent studies suggest that the genetic polymorphisms are linked with development of schizophrenia.
Polymorphisms of schizophrenia susceptibility and different cytokine genes act as the genetic markers. The objective of our
study is to examine the association between the neuregulin 1 and tumor necrosis factor-α (−308) gene polymorphism with schizophrenia. This association was performed on the basis of molecular biology to screen
the mutations of neuregulin 1 and tumor necrosis factor-α (−308) gene in schizophrenic patients by polymorphism analysis. Statistical analysis of the observed data shows that there
was an association (P = 0.003) between patient’s group and controls in terms of genotypes of single-nucleotide polymorphism 1 rather than single-nucleotide
polymorphism 2 of neuregulin 1. So, heterozygous (adenine/guanine) allelic pattern can be a higher risk factor of schizophrenic patients. Polymorphism
of tumor necrosis factor-α (−308) gene indicated frequent presence of homozygous (adenine/adenine) allelic pattern in patient’s group than in controls
(P = 0.015). Statistical analysis indicates that the age distribution has significant difference between patient’s group and
controls (P = 0.022) while the gender ratio is not significantly different (P = 0.366) between the two groups. It was concluded that in Pakistani population the neuregulin 1 and tumor necrosis factor-α (−308) genes are strongly associated with schizophrenia. 相似文献
4.
Kevin Morgan Linda Morgan Karen Carpenter James Lowe Letty Lam Samantha Cave John Xuereb Claude Wischik Charles Harrington N. A. Kalsheker 《Human genetics》1996,99(1):27-31
A variant of the apolipoprotein E gene, APOE*4, is associated with both sporadic Alzheimer’s disease (AD) and a subset of
familial AD and this association is stronger with early as opposed to late onset AD. Both APOE*4 and α1-antichymotrypsin (ACT) will accelerate the rate of amyloid filament formation and are major constituents of the plaques associated
with AD. We now show that a dinucleotide microsatellite allele in the 5′-flanking sequence of the ACT gene, designated A10,
in association with APOE*4 significantly increases the risk of developing sporadic AD, which accounts for the majority of
AD cases.
Received: 15 May 1996 / Revised: 7 July 1996 相似文献
5.
Tumor necrosis factor-alpha (TNF-α) has been regarded as a candidate gene for Crohn’s disease (CD) based on its inflammatory function in immune reaction and
the clinical effectiveness of anti-TNF-α therapy. However, studies to date have reported inconsistent findings for the association
between TNF-α and CD. The PubMed, EMBASE, and Medline databases were systematically reviewed from all English language publications
up to April, 2011. A total of twenty-nine studies concerning the association between CD and the TNF-α promoter polymorphisms of −308G/A, −857C/T and −238G/A were identified, among of them only twenty-three studies match the
inclusion criteria (including 3,843 cases and 6,260 controls) and were selected for the statistical test. We found that neither
the G allele of −308G/A (OR 1.02, 95% CI 0.87–1.19, P = 0.84), C allele of −857C/T (OR 0.97, 95% CI 0.86–1.09, P = 0.57) and G allele of −238G/A (OR 0.91, 95% CI 0.70–1.18, P = 0.48), and nor their GG (OR 1.05, 95% CI 0.88–1.25, P = 0.59), CC (OR 0.98, 95% CI 0.86–1.12, P = 0.76) and GG (OR 0.92, 95% CI 0.70–1.21, P = 0.55) genotypes were associated with CD susceptibility, respectively. Our meta-analysis demonstrates that three promoter
polymorphisms of TNF-α above may not confer susceptibility to CD. 相似文献
6.
7.
A. M. W. Coppus D. Fekkes W. M. A. Verhoeven S. Tuinier C. M. van Duijn 《Amino acids》2010,38(3):923-928
Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected
with Alzheimer’s disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present
study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and
related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of
healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an
increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations
correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (ρ = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD. 相似文献
8.
9.
No consensus has been recently reached at the relationship between the α1-antichymotrypsin (ACT) signal peptide −15A/T polymorphism
and Alzheimer’s disease (AD) risk. Thus, our study aimed to better assess this association by performing a meta-analysis,
including 4,212 cases and 4,039 controls from 29 studies. Odds ratios (ORs) with the 95% confidence interval (CI) were used
to assess the strength of relationship between ACT −15A/T polymorphism and AD risk. Overall, a borderline statistically significant
association was detected under recessive model comparison in all subjects (AA vs. AT+TT: OR 1.12, 95% CI 1.01–1.25, P = 0.04). But in subgroup analysis by ethnicity, no significant association was found in Caucasians, Asians, or Africans.
Moreover, after exclusion of one study which affect the heterogeneity, the ACT A allele and AA genotype were statistically
associated with late-onset AD (LOAD) risk (AA vs. TT: OR 1.25, 95% CI 1.06–1.48, P = 0.007, A vs. T: OR 1.12, 95% CI 1.03–1.21, P = 0.008), especially in Caucasians. In conclusion, our study suggests that the common α1-antichymotrypsin signal peptide
−15A/T polymorphism may not be a major risk factor for AD. However, the polymorphism is capable of increasing LOAD risk. 相似文献
10.
Although Niemann-Pick C1 disease has frequently been called “juvenile Alzheimer’s”, the effects of introducing Npc1 mutations into a mouse model of Alzheimer’s have not previously been performed. We have crossed Npc1
+/− mice with APP/PS1 “Alzheimer’s” mice and studied Aβ42 accumulation and amyloid plaque formation. Mice heterozygous for Npc1 and positive for the APP and PS1 transgenes accumulated Aβ42 more rapidly than the APP/PS1 controls and this correlated,
as expected, with the area of amyloid plaques. We conclude that the alterations of intracellular cholesterol present in Npc1
+/− mice can influence the progress of Alzheimer’s disease in the APP/PS1 mouse model. 相似文献
11.
Matthew Schrag April Dickson Arshad Jiffry David Kirsch Harry V. Vinters Wolff Kirsch 《Biometals》2010,23(6):1123-1127
Reports that iron, zinc and copper homeostasis are in aberrant homeostasis are common for various neurodegenerative diseases,
particularly for Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease. Manipulating the levels of these elements
in the brain through the application of chelators has been and continues to be tested therapeutically in clinical trials with
mixed results. Much of the data indicating that these metals are abnormally concentrated in Alzheimer’s disease and Parkinson’s
disease brain tissue was generated through the analysis of post-mortem human tissue which was archived in formalin. In this
study, we evaluated the effect of formalin fixation of brain on the levels of three important transition metals (iron, copper,
and zinc) by atomic absorption spectroscopy. Paired brain specimens were obtained at autopsy for each case; one was conserved
by formalin archival (averaging four years), the other was rapidly frozen. Both white and grey matter samples were analyzed
and the concentrations of iron and zinc were found to decrease with fixation. Iron was reduced by 40% (P < 0.01), and zinc by 77% (P < 0.0001); copper concentrations increased by 37% (P < 0.05) by the paired T-test. The increase in copper is likely due to contamination from trace copper in the formalin. These
results indicate that transition metal data obtained from fixed tissue may be heavily distorted and care should be taken in
interpreting this data. 相似文献
12.
Alzheimer’s disease is a 100-year-old concept. As a diagnostic label, it has evolved over the 20th and 21st centuries from
a rare diagnosis in younger patients to a worldwide epidemic common in the elderly, said to affect over 35 million people
worldwide. In this opinion piece, we use a constructivist approach to review the early history of the terms “Alzheimer’s disease”
and related concepts such as dementia, as well as the more recent nosological changes that have occurred in the four major
editions of the Diagnostic and Statistical Manual since 1952. A critical engagement of the history of Alzheimer’s disease and dementia, specifically the evolution of those
concepts in the DSM over the past 100 years, raises a number of questions about how those labels and emergent diagnoses, such
as Neurocognitive Disorders and Mild Cognitive Impairment, might continue to evolve in the DSM-V, due for release in 2013. 相似文献
13.
Chistiakov DA Voronova NV Turakulov RI Savost'anov KV 《Journal of applied genetics》2011,52(2):201-207
The human secretoglobin 3A2 (SCGB3A2) gene encoding secretory uteroglobin-related protein 1 (UGRP1) resides on the chromosome region 5q31-33 that harbors a susceptibility
locus to several autoimmune and inflammatory diseases, including asthma and Graves’ disease (GD). Recently, association between
the marker rs1368408 (−112G > A), located in the promoter region of the SCGB3A2 gene, and susceptibility to GD was found in Chinese and UK Caucasians. The study aim was to evaluate whether this polymorphism
confers GD susceptibility in a large population cohort comprising 1,474 Russian GD patients and 1,619 controls. The marker
rs1368408 was studied using a TaqMan allele discrimination assay. Serum levels of UGRP1 and immunoglobulin E (IgE) were assessed
using enzyme-linked immunosorbent assay (ELISA) analyses. Association between the allele A of SCGB3A2 and a higher risk of GD (odds ratio [OR] = 1.33, P = 2.9 × 10−5) was shown. Both affected and non-affected carriers of the higher risk genotype A/A had significantly decreased levels of
serum UGRP1 compared to the subjects homozygous for G/G (93 ± 37 pg/ml vs. 132 ± 45 pg/ml, P = 0.0011 for GD patients; 77 ± 28 pg/ml vs. 119 ± 33 pg/ml, P = 0.0019 for controls). Serum IgE levels were significantly higher in non-affected subjects homozygous for A/A compared to
control individuals homozygous for G/G (153 ± 46 IU/ml vs. 122 ± 40 IU/ml, P = 0.0095). Our data suggest that the carriage of the SCGB3A2 −112A/A variant increases the risk for GD in subsets of patients with elevated levels of IgE, a hallmark of allergic asthma.
Therefore, the SCGB3A2 −112G > A polymorphism may be considered as a likely marker linking susceptibility to allergy/asthma and GD on chromosome
5q31-33. 相似文献
14.
The association between apolipoprotein E (APOE) epsilon 4 (ε4) allele and outcomes of traumatic spinal cord injury (SCI) is
still controversial and ambiguous. The objective of this study was to test the hypothesis that APOE polymorphisms are associated
with outcomes after SCI in Chinese Han patients. APOE polymorphisms were determined in 100 patients with cervical SCI (C3–C8).
The genotype frequency of this polymorphism was determined by using a polymerase chain reaction-restriction fragment length
polymorphism assay. Patients with an APOE ε4 allele had significantly less motor recovery during rehabilitation than did patients
without an APOE ε4 allele (mean 3.7 vs. 6.1; P = 0.04) and a longer rehabilitation length of stay (LOS) (mean 117.4 vs. 94.5; P = 0.02), but better sensory-pinprick recovery (mean 6.1 vs. 4.0; P = 0.03). There were no significant differences by APOE ε4 allele status in sensory-light touch recovery or acute LOS. This
study suggests that the APOE ε4 allele is associated with outcomes after SCI and longer rehabilitation LOS in Chinese Han
patients. 相似文献
15.
Pietras T Szemraj J Panek M Witusik A Banasiak M Antczak A Górski P 《Molecular biology reports》2012,39(3):2163-2167
Cyclooxygenase two (COX-2) is an important enzyme metabolizing arachidonic acid. In contrast to constitutive cyclooxygenase
one (COX-1), COX-2 is induced by proinflammatory factors. Polymorphism −765G/C in COX-2-encoding gene promoter is associated
with development of Alzheimer’s disease, depression, carcinoma of the pancreas in smokers, breast cancer and rheumatoid arthritis.
It is interesting whether the −765G/C polymorphism in COX-2-encoding gene promoter can be associated with COPD, a disease
which is inflammatory in character. It is highly probable as the breast and pancreas cancers, whose associations with the
analyzed polymorphism have been studied, are smoking-dependent tumors. Additionally, tobacco smoke has been demonstrated to
induce COX-2 in the lungs. The study group consisted of 122 COPD patients (48 females, 74 males). The control group consisted
of 149 healthy nonsmoking subjects (83 females, 66 males). Polymerase chain reaction/restriction fragment length polymorphism
was used for genotyping. A statistically significant difference in genotype distribution was observed as a result of the comparison
between healthy subjects and patients with COPD. The distribution of alleles in both groups conformed with Hardy–Weinberg
equilibrium. In the group of COPD patients, GG allele was found in 79 subjects, GC in 36, and CC in 7 subjects (F = 0.094,
P = 0.296927); in the control group, 73 subjects had GG allele, 68—GC and 8—CC (F = 0.12728, P = 0.120265). The allele frequency revealed differences between those groups, attaining the level of statistical significance
(χ2 = 29.043, df = 2, P = 0.0000. The carriers of −765G allele are at 1.53-fold higher risk of developing COPD. The presence of GG genotype does
not increase significantly the risk of the disease. It is also noteworthy that the carriers of CC or GC genotypes are at significantly
lower risk of developing COPD than the group of subjects with GG genotype. 相似文献
16.
The aim of this study was to identify candidate causal single nucleotide polymorphisms (SNPs) and candidate causal mechanisms
of psoriasis and Behcets’s disease (BD) and to generate an SNP → gene → pathway hypothesis. A psoriasis genome-wide association
study (GWAS) dataset that included 436,192 SNPs in 1,409 psoriasis cases and 1,436 controls of European descent and a BD GWAS
dataset that contained 310,324 SNPs in 1,215 BD cases and 1,278 controls were used in this study. Identify candidate causal
SNPs and pathways (ICSNPathway) analysis was applied to the GWAS datasets. ICSNPathway analysis identified 15 candidate causal
SNPs and 28 candidate causal pathways. The top five candidate causal SNPs were rs1063478 (P = 1.45E−10), rs8084 (P = 2.20E−08), rs7192 (P = 5.18E−08), rs20541 (P = 5.30E−06), and rs1130838 (P = 5.65E−06), which with the exception of rs20541 [interleukin (IL)-13] are at human leukocyte antigen (HLA) loci. These candidate
causal SNPs and pathways provided ten hypothetical biological mechanisms. The most strongly associated pathway concerned HLA.
When HLA loci were excluded, ICSNPathway analysis provided one hypothetical biological mechanism. rs20541 (non_synonymous_coding) → IL-13 → dendritic
cell involvement in the regulation of Th1 and Th2 development, and the GATA3 pathway. ICSNPathway analysis identified four
candidate causal SNPs, eleven candidate causal pathways, and three hypothetical biological mechanisms. One of them was as
follows: rs2072895 (non_synonymous_coding & splice-site) and rs2735059 (non_synonymous_coding) → HLA-F → type I diabetes mellitus,
antigen processing and presentation, and autoimmune thyroid disease. The application of ICSNPathway analysis to GWAS dataset
of psoriasis and BD resulted in the identification of candidate causal SNPs and candidate pathways that might contribute to
psoriasis susceptibility. 相似文献
17.
To investigate whether there is any association between various APOE alleles and factor V Leiden (FVL) with lipid profiles
and sickle cell disease (SCD) in Southern Iran. 65 SCD patients consisting of 35 sickle cell anemia homozygous (SS), 15 sickle
cell heterozygous (AS) and 15 sickle cell/βThalassemia (S/βthal) patients and 68 healthy individuals with normal hematological
indices were studied. APOE and FVL polymorphisms were detected by PCR–RFLP and serum lipid level was measured enzymatically.
The frequencies of FVL and APOE-ε4 allele were significantly higher in SCD patients than in control (15.4 vs. 4.4 and 13.7%
vs. 3.3%, respectively). The distributions of APOE ε3ε3, ε2ε3 and ε2ε4 + ε3ε4 alleles in SCD patients were significantly different
from those in the control group. The SCD subjects particularly SS/S βthal (SS + S/βthal) and SS patients have significantly
lower frequency of APOE ε3ε3 allele (P < 0.05) whereas SCD, SS patients and AS individuals have a significantly higher frequency of APOE ε4 allele (ε2ε4 + ε3ε4;
P = 0.003, P = 0.011 and P = 0.035, respectively) compared to the control group. The LDL-C (P = 0.006) and total cholesterol (P < 0.001) levels in SCD subjects were found to be significantly lower than those in the control group. In addition, the presence
of non-APOE ε4 allele (ε2ε3 + ε3ε3) resulted in a significant decrease in the level of LDL-C and total cholesterol in SCD
subjects in general and in SS and SS/S βthal patients in particular compared to controls. Furthermore, the presence of APOE
ε4 allele (ε2ε4 + ε3ε4) was found to be associated with the risk of sickle cell anemia [OR = 4.1, P = 0.04]. The presence of either FVL mutation (OR = 4.6; CI: 0.91–24, P = 0.07) or APOE-ε4 allele (OR = 4.07; CI: 1.01–16.4, P = 0.048) is associated with the risk of sickle cell disease in Southern Iran. This data suggest that the activation of coagulation
system enhances thrombus generation and decreases antioxidant activity in SCD patients from Southern Iran. 相似文献
18.
Pomara N Bruno D Nierenberg JJ Sidtis JJ Martiniuk FT Mehta PD Zetterberg H Blennow K 《Neurochemical research》2011,36(6):1124-1128
A variable poly-T polymorphism in the TOMM40 gene, which is in linkage disequilibrium with APOE, was recently implicated with
increased risk and earlier onset age for late-onset Alzheimer’s disease in APOE ε3 carriers. To elucidate potential neurobiological
mechanisms underlying this association, we compared the effect of TOMM40 poly-T variants to the effect of APOE, an established
LOAD-risk modulator, on cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels, in cognitively intact elderly subjects. APOE ε4 carriers showed significant reductions in Aβ 1-42 levels compared to non-ε4 carriers, but no differences were detected across TOMM40 variants. Neither Aβ 1-40 nor tau levels were affected by APOE or TOMM40. 相似文献
19.
Mizuta I Tsunoda T Satake W Nakabayashi Y Watanabe M Takeda A Hasegawa K Nakashima K Yamamoto M Hattori N Murata M Toda T 《Human genetics》2008,124(1):89-94
Parkinson’s disease (PD), one of the most common human neurodegenerative disorders, is characterized by the loss of dopaminergic
neurons in the substantia nigra of the midbrain. Our recent case-control association study of 268 SNPs in 121 candidate genes
identified α-synuclein (SNCA) as a susceptibility gene for sporadic PD (P = 1.7 × 10−11). We also replicated the association of fibroblast growth factor 20 (FGF20) with PD (P = 0.0089). To find other susceptibility genes, we added 34 SNPs to the previous screen. Of 302 SNPs in a total 137 genes,
but excluding SNCA, SNPs in NDUFV2, FGF2, CALB1 and B2M showed significant association (P < 0.01; 882 cases and 938 control subjects). We replicated the association analysis for these SNPs in a second independent
sample set (521 cases and 1,003 control subjects). One SNP, rs1805874 in calbindin 1 (CALB1), showed significance in both analyses (P = 7.1 × 10−5; recessive model). When the analysis was stratified relative to the SNCA genotype, the odds ratio of CALB1 tended to increase according to the number of protective alleles in SNCA. In contrast, FGF20 was significant only in the subgroup of SNCA homozygote of risk allele. CALB1 is a calcium-binding protein that widely is expressed in neurons. A relative sparing of
CALB1-positive dopaminergic neurons is observed in PD brains, compared with CALB1-negative neurons. Our genetic analysis suggests
that CALB1 is associated with PD independently of SNCA, and that FGF20 is associated with PD synergistically with SNCA.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
20.
Vaisi-Raygani A Rahimi Z Tavilani H Vaisi-Raygani H Kiani A Aminian M Shakiba E Shakiba Y Pourmotabbed T 《Molecular biology reports》2012,39(3):2723-2731
We have previously shown that angiotensin-converting enzyme (ACE) gene D allele is an independent risk factor for early onset
coronary artery disease (CAD). Little is known about the concomitant presence of the ACE gene D allele and paraoxonase (PON1)
codon 192 arginine (Arg) on the severity of CAD. Regarding the high rate of CAD among Iranians the aim of present study was
to examine the hypothesis of synergistic effects between ACE-D and PON1-Arg alleles on predisposition and the severity of
CAD in our population. The PON1 192 and ACE insertion/deletion (I/D) genotypes were detected by PCR-RFLP and PCR, respectively
in 414 individuals undergoing their first coronary angiography. Patients were placed into one of two groups: CAD and control
without CAD or diabetes. We mentioned the synergistic effects of both genes and not ACE gene alone is a risk factor for CAD.
We found that PON1 Arg 192 and ACE D allele act synergistically to increase the risk of CAD (OR 1.3, P = 0.044). Our results showed a significant correlation between the possession of both PON1 192 Arg and the ACE D allele and
the extent of CAD in CAD patients and CAD subjects without diabetes, represented by the increased frequency of three-vessel
disease with OR 2.7, P = 0.046; χ2 = 4, P = 0.046 and OR 2.4, P = 0.051; χ2 = 3.8, P = 0.051, respectively. We found that PON1 Arg 192 and ACE D alleles act synergistically to increase the risk of CAD in CAD
patients and CAD subjects without diabetes from west of Iran, who have high frequency of three-vessel disease. Our data suggest
that PON1 192 Arg and the ACE D allele in combination with each other can be important independent risk factor for severity
of CAD in patients carrying both PON1 192 Arg and the ACE D allele in a west population of Iran. 相似文献