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1.
BackgroundInfluence of folate/homocysteine conversion is considered to be important in the pathogenesis of Parkinson's disease (PD). However, association of the folate metabolic pathway gene polymorphisms with PD susceptibility remains unclear.MethodsTo test this possibility in PD, we conducted a hospital-based case-control study constituting 211 patients and 218 age- and sex-matched controls of ethnic Chinese in Taiwan. Genotyping assay was performed to screen for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR A1049G and C1783T) genes and assess the association between these genotype polymorphisms and PD risk using logistic regression analysis.ResultsOf these four non-synonymous polymorphisms, the MTRR 1049GG variant was significantly associated with PD susceptibility (OR = 3.17, 95%CI = 1.08–9.35). Furthermore, we stratified our patients based on the MTHFR 677TT genotype in different strata, a significant association between the joint effect of polymorphisms and PD risk was observed in those patients whose genotypes were MTRR A1049G/MTR A2756G or MTRR C1783T/MTR A2756G (P < 0.05).ConclusionOur findings provide support for the synergistic effects of polymorphisms in the folate metabolic pathway genes in PD susceptibility; the increased PD risk would be more significant in carriers with the polymorphisms of MTHFR, MTR, and MTRR genes.  相似文献   

2.
We studied the diversity of bacteria and host in the H. pylori-human model. The human indigenous bacterium H. pylori diverged along with humans, into African, European, Asian and Amerindian groups. Of these, Amerindians have the least genetic diversity. Since niche diversity widens the sets of resources for colonizing species, we predicted that the Amerindian H. pylori strains would be the least diverse. We analyzed the multilocus sequence (7 housekeeping genes) of 131 strains: 19 cultured from Africans, 36 from Spanish, 11 from Koreans, 43 from Amerindians and 22 from South American Mestizos. We found that all strains that had been cultured from Africans were African strains (hpAfrica1), all from Spanish were European (hpEurope) and all from Koreans were hspEAsia but that Amerindians and Mestizos carried mixed strains: hspAmerind and hpEurope strains had been cultured from Amerindians and hpEurope and hpAfrica1 were cultured from Mestizos. The least genetically diverse H. pylori strains were hspAmerind. Strains hpEurope were the most diverse and showed remarkable multilocus sequence mosaicism (indicating recombination). The lower genetic structure in hpEurope strains is consistent with colonization of a diversity of hosts. If diversity is important for the success of H. pylori, then the low diversity of Amerindian strains might be linked to their apparent tendency to disappear. This suggests that Amerindian strains may lack the needed diversity to survive the diversity brought by non-Amerindian hosts.  相似文献   

3.
BackgroundMembranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in adults. NPHS1 encoding nephrin is a transmembrane protein of the immunoglobulin family. We clarified the relationship between NPHS1 gene polymorphisms and the susceptibility or progression of MGN.MethodsWe recruited a cohort of 132 biopsy-diagnosed MGN patients and 257 healthy subjects. Genotyping of three SNPs (rs401824, rs437168 and rs3814995) at chromosome positions 41034749 (5′UTR), 41026259(exon17) and 41034052 (exon 3) was performed using a Taqman SNP genotyping assay.ResultsThere was a significant difference in genotype frequency distribution of rs437168 polymorphism between MGN patients and controls. The results also showed that the frequency of the G allele was significantly higher in the patient group. Among the polymorphisms rs437168, rs401824 and rs3814995, no significant haplotype was shown in MGN patients. A stratified analysis revealed that a high disease progression in the AA genotype of rs401824 and GG genotype of rs437168 patients were associated with a low rate of remission.ConclusionsThe presence of the different genotypes of NPHS1 was associated with susceptibility of MGN and the remission of proteinuria during disease progression after the therapy.  相似文献   

4.
ObjectivesTo investigate the polymorphism distribution of Val-9Ala and Ile + 58Thr of the Mn-superoxide dismutase (Mn-SOD) gene among subjects with Parkinson's disease (PD) by analyses of genders and clinical severity.Design and MethodsWe examined the DNA genotypes of Val-9Ala and Ile + 58Thr from 295 PD subjects and 111 controls by nucleotide sequencing and BsaWI restriction.ResultsAla/Ala homozygosity was found in four PD subjects but not in the controls. All of the genotypes at codon + 58 among the examined samples were Ile/Ile homozygotes. Although higher carrier rate of Ala allele among PD subjects than the controls, there were no differences by analyses of the genders and clinical severity.ConclusionThe higher Ala-allele carrier rate among PD subjects may suggest a possible higher amount of mitochondrial Mn-SOD rendering higher intracellular stress in PD. In this study the polymorphisms at codons -9 and + 58 did not give informative association evidences with PD.  相似文献   

5.
ObjectivesParaoxonase (PON1) plays a role in preventing the oxidation of lipoproteins and protecting against atherosclerosis. Several polymorphisms have been described in the gene encoding this enzyme, which are related to different enzymatic activities. Fabry Disease (FD) is a lysosomal storage disease associated with cardiomyopathy, early-onset stroke, renal failure, among other features. The objective of the current study was to investigate the PON1 polymorphisms Gln192Arg and Leu55Met in FD patients and correlate them with clinical symptoms.Design and methodsA total of 106 subjects with FD and 26 healthy individuals were selected for the study. Both polymorphisms were assessed in the DNA of blood samples using PCR-RFLP. Hardy–Weinberg equilibrium was calculated for the genotypes and statistical analyses were realized using the Chi-Squared test with Yates correction.ResultsThe allele frequencies of the polymorphism Gln192Arg for FD patients and control were 0.38 and 0.25, respectively. A comparison of the frequencies for Gln192Arg polymorphism between FD patients and controls revealed a significant difference. The clinical information was obtained from 41 patients. Patients with the Gln192Arg polymorphism showed different cardiovascular manifestations.ConclusionsThe higher frequency of the Gln192Arg polymorphism among FD patients highlighted the possibility of a correlation between the PON1 genetic variation and the phenotypes because the disease has a wide range of symptoms not explained exclusively by mutations on the GLA gene.  相似文献   

6.
ObjectiveSeveral studies have reported the association of genes related to vascular tone, hypertension, oxidative stress and preeclampsia. We investigated the possible association among three polymorphisms in eNOS (as well their haplotypes): one of MTHFR, one of GSTP1 and one of AGT, with severe preeclampsia in Mexican-Mestizo women.MethodsTwo hundred thirty women with severe preeclampsia and 350 control subjects were genotyped; for rs2070744 and rs1799983 of eNOS, rs1801133 of MTHFR, rs1695 of GSTP1 and rs699 of AGT we used real-time PCR allelic discrimination and for VNTR of eNOS, PCR. Allele frequency differences were assessed by χ2. Logistic regression was used to test for associations and for haplotype frequencies using Haploview 4.2.ResultsGenotypic and allelic distribution of the polymorphisms was similar between cases and controls; likewise, haplotype frequencies of the three polymorphisms of eNOS did not differ significantly.ConclusionsTo our knowledge, this is the first time that these polymorphisms have been analyzed together and exclusively in women with severe preeclampsia. However, we did not find an association between polymorphisms of eNOS, MTHFR, GSTP1 and AGT with severe preeclampsia in our population. Additionally, we observed differences in the distribution of the alleles and genotypes of these polymorphisms in our population in comparison to those described in other ethnic groups.  相似文献   

7.
ObjectiveAbnormal B cell lymphoma-2 (Bcl-2) and interleukin-19 (IL-19) expression is closely related to systemic lupus erythematosus (SLE) pathogenesis. We aimed to determine whether BCL2 polymorphisms and a single nucleotide polymorphism (SNP) of IL19 are significantly associated with SLE susceptibility and if this is affected by synergism between IL19 and BCL2 genotypes.MethodsThis observational cohort study randomly enrolled 150 patients with SLE and 150 healthy controls. Major BCL2 and IL19 allele and genotype distributions were examined in the two groups. The IL19 SNP rs2243188 was determined using the TaqMan-MGB probe method. The synergistic effect between BCL2 and IL19 and clinical symptoms of SLE was also analyzed.ResultsThe distribution of major BCL2 genotypes and common BCL2 alleles, especially for genotypes 191, 193, and 197, differed significantly between patients and controls. A significant difference in the dominant genetic model was also observed between groups, but not in the recessive model. The risk of disease in individuals who carried both 195-bp BCL2 and 138-bp IL19 susceptibility alleles was higher than in those carrying either allele alone.ConclusionsThis preliminary study suggested that BCL2 polymorphisms and the IL19 SNP rs2243188 are closely related to the pathogenesis of SLE.  相似文献   

8.
BackgroundOxygen uptake efficiency slope (OUES) is a method for investigating cardiorespiratory fitness and is proposed as an alternative to overcome the limitations of traditional measures such as peak oxygen consumption (VO2peak) for patients who do not achieve a maximum response, such as in Parkinson's disease (PD).ObjectiveTo assess the performance of individuals with PD during the six-minute walk test (6MWT) using the OUES.MethodsThis is an observational cross-sectional study including 12 individuals with PD and 12 healthy controls. Participants performed the 6MWT along with an analysis of exhaled gas kinetics. The OUES was determined from the last 16 s of the walk test. Multiple linear regression analyses were computed to explore associations between the independent (OUES) and the dependent variables (VO2peak) controlled by group.ResultsThe OUES was associated to VO2peak on the 6MWT (β=0.24, p<0.01) in individuals with PD. The PD group had low performance on the 6MWT with a shorter distance walked (mean difference: -113.1 m; 95% CI: -203.2, -59.1) and worse cardiopulmonary condition with lower OUES values (mean difference: -0.52 [l/minO2]/[l/minVE]; 95% CI: -0.83, -0.21) found in this same group.ConclusionsOur results suggest that OUES is related to VO2peak during the 6MWT, and therefore it could be used as a submaximal test evaluation tool which provides cardiopulmonary reserve data in individuals with PD.  相似文献   

9.
BACKGROUND: Apolipoprotein E polymorphisms have important effects on plasma lipid levels and in the genetic susceptibility to development of cardiovascular diseases. Thus, the purpose of this study was to investigate the association of apolipoprotein E polymorphisms with coronary artery disease and with plasma lipid levels in a group of Mexican Mestizo patients. METHODS: Apolipoprotein E polymorphisms were determined in 156 Mexican patients with coronary artery disease and 200 non-related healthy controls using the restriction fragment length polymorphism technique. The correlation of these polymorphisms with lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in the patient group was determined. RESULTS: A similar distribution of allele and genotype frequencies in coronary artery disease patients and healthy controls was found. Higher serum levels of high-density lipoprotein cholesterol and lower levels of low-density lipoprotein cholesterol, triglycerides and glucose were found in patients with the APOE*2/3 genotype when compared to patients with the APOE*3/4 and APOE*3/3 genotypes, although these differences were not significant. CONCLUSIONS: Our data suggest that genetic variation at the APOE is not a genetic factor related to the genetic susceptibility to coronary artery disease in Mexican individuals, but the role of this polymorphism in determining the lipid profile cannot be excluded.  相似文献   

10.
BackgroundAbnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. We examined whether 2 MMP-9 polymorphisms (C? 1562 T and (CA)n) and haplotypes are associated with preeclampsia and/or gestational hypertension.MethodsWe studied 476 pregnant women: 176 healthy pregnant (HP), 146 pregnant with gestational hypertension (GH), and 154 pregnant with preeclampsia (PE). Genomic DNA was extracted from whole blood and genotypes for C? 1562 T and (CA)n polymorphisms were determined by PCR-RFLP. Haplotype frequencies were inferred using the PHASE ver. 2.1 program.ResultsFor the g.?90(CA)13–25 polymorphism, no significant differences were found in genotype and allele distributions when PE or GH groups were compared with HP group. However, the CT genotype and T allele for g.?1562C > T polymorphism were more commonly found in GH subjects compared with the HP group (both P < 0.05). Conversely, we found no differences in genotypes or allele distributions for the g.?1562C > T polymorphism when the PE and the HP groups were compared. No significant differences were found in overall distributions of haplotype frequencies when the GH or the PE group was compared with the HP group.ConclusionsThe C? 1562 T polymorphism in MMP-9 gene is associated with gestational hypertension, but not with preeclampsia. These findings may help to explain the higher plasma MMP-9 levels previously reported in GH compared with HP.  相似文献   

11.
BackgroundMembranous glomerulonephritis (MGN) is one of common causes of idiopathic nephrotic syndrome in adults, and 25% of MGN patients proceed to end-stage renal disease. STAT4 gene polymorphisms have been reported to be associated with many inflammatory diseases. The objective of this study was to clarify the relationship between STAT4 gene polymorphisms and the pathogenesis of MGN.MethodsWe investigated the association of three STAT4 gene polymorphisms (rs3024912, rs3024908, and rs3024877) with the susceptibility to MGN in 403 Taiwanese populations (138 MGN patients and 265 controls).ResultsThe results indicated that the statistically significant difference in genotype frequency distribution was found at rs3024908 SNP in MGN patients and control groups (p = 0.014). In addition, the individuals with the GG genotype at rs3024912 SNP may have a higher risk in kidney failure of MGN patients (adjusted odds ratio [OR] = 3.255; 95% confidence interval [CI] = 1.155–9.176, p = 0.026).ConclusionsOur data provide a new information that the STAT4 (rs3024912 and rs3024908) polymorphisms may be the underlying cause of MGN, and these polymorphisms revealed by this study warrant further investigation.  相似文献   

12.
BackgroundType 2 of diabetes is the most common metabolic disorder and results from the interaction between genetic and environmental factors. Insulin receptor substrate-2 (IRS-2), one of the major substrates of the insulin receptor, has a crucial role in insulin signalling and in beta cell development and survival. While several polymorphisms have been identified in the IRS-2 gene, the association of the Gly1057Asp polymorphism with type 2 diabetes has been studied in European and Chinese populations, but the results have been inconsistent.ObjectivesThe aim of this study was to investigate the association of Gly1057Asp polymorphism in insulin receptor substrate-2 (IRS-2) gene among patients with type 2 diabetes in well defined ethnic groups from Djerba Island in Southeastern Tunisia.MethodsThe studied population (172 Arabs and 100 Berbers) includes 162 patients with type 2 diabetes and 110 healthy controls. BMI was calculated for each subject. The subjects were unrelated and randomly selected Arabs and Berbers were equally distributed between controls and diabetics. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay.ResultsThis case/control study indicated that frequency of the IRS-2 Gly1057Asp polymorphism was not significantly different between the healthy controls and type 2 diabetic groups, neither between healthy nor obese subjects, in both ethnic groups. Moreover, this polymorphism is present at a lower frequency in Djerbian than in neighbouring European populations.ConclusionThese results strongly argue against a major role of the Gly1057Asp IRS-2 polymorphism in the pathogenesis of type 2 diabetes in Djerbian subjects.  相似文献   

13.
BackgroundsGlimepiride is a commonly used sulfonylurea hypoglycemic agent. There is considerable interindividual variation in the response to sulfonylurea for patients with type 2 diabetes. The purpose of this study was to investigate whether genetic variations influence the efficacy of glimepiride in healthy Korean subjects.MethodsA single 2-mg oral dose of glimepiride was administered to 46 healthy volunteers. Serial blood sampling for 12 h after oral dosing was performed for determination of plasma glimepiride, glucose and insulin levels. We tested the association of seven single nucleotide polymorphisms (SNPs) in four candidate genes with the efficacy of glimepiride.ResultsPharmacodynamic profiles for plasma glucose and insulin showed no statistically significant differences among genotype groups, and parameters were not different from one another. There were no association of the KCNJ11, NOS1AP, TCF7L2 and ABCC8 gene polymorphisms and the efficacy of glimepiride.ConclusionsKnowledge of these polymorphisms provides no clinical useful information for the pharmacogenetic therapeutic approach for Korean patients with type 2 diabetes.  相似文献   

14.
BackgroundMyeloperoxidase (MPO) has been listed as a potentially useful risk marker in acute coronary syndrome. However, its clinical utility in patients with acute chest pain is not yet defined.Design and methodsMPO (Architect, Abbott Diagnostics) was measured in 120 healthy controls and 303 chest pain patients who had been admitted to the coronary care units of three Swedish hospitals.ResultsChest pain patents had significantly higher median MPO levels compared to healthy controls (120.6 vs. 78. 9 pmol/L; p < 0.001). However, MPO was not useful for the diagnosis of myocardial infarction (c-statistics 0.61 [95% CI 0.54–0.67]), and Cox regression analysis revealed no independent association between MPO and mortality (adjusted hazard ratio 1.3 [95% CI 0.8–2.0]) or the composite endpoint (adjusted hazard ratio 1.1 [95% CI 0.8–1.5]) after a median follow-up of 4.9 years.ConclusionsMPO provided no clinically relevant information in the present population of chest pain patients.  相似文献   

15.
ObjectiveThe aim of this study was to determine the relationship between joint position sense and static and dynamic balance in female patients with chronic neck pain compared with healthy controls.MethodsThe study sample comprised 25 female patients with chronic neck pain and 25 healthy (asymptomatic) female controls. Pain severity with the visual analog scale, joint position sense with the laser pointer method, static balance with the Single-Leg Balance Test, and dynamic balance with the Y Balance Test were assessed.ResultsThe deviation in cervical joint position sense was greater in extension (P < .001), right rotation (P < .001), and left lateral rotation (P < .05) in the patients with chronic neck pain compared with the healthy controls. The results of the patients with chronic neck pain were worse than the healthy controls in the Single-Leg Balance Test with both eyes open (P < .05) and eyes closed (P < .05). The patients with chronic neck pain had worse dynamic balance only in the anterior direction reach of the left leg (P < .05).ConclusionCervical joint position sense and static balance were worse in female patients with chronic idiopathic neck pain when compared with asymptomatic controls. Dynamic balance in all other directions except for the anterior direction was not negatively affected in individuals with chronic idiopathic neck pain.  相似文献   

16.

Background:

Outcomes for peritoneal dialysis (PD) patients are affected by the characteristics of the peritoneal membrane, which may be determined by genetic variants. We carried out a systematic review of the literature to identify studies which assessed the association between genetic polymorphisms, peritoneal membrane solute transport, and clinical outcomes for PD patients.

Methods:

The National Library of Medicine was searched using a variety of strategies. Studies which met our inclusion criteria were reviewed and data abstracted. Our outcomes of interest included: high transport status peritoneal membrane, risk for peritonitis, encapsulating peritoneal sclerosis (EPS), patient and technique survival. We combined data from studies which evaluated the same genetic polymorphism and the same outcome.

Results:

We evaluated 18 relevant studies. All studies used a candidate gene approach. Gene polymorphisms in the interleukin (IL)-6 gene were associated with peritoneal membrane solute transport in several studies in different ethnic populations. Associations with solute transport and polymorphisms in endothelial nitric oxide synthase and receptor for advanced glycation end product genes were also identified. There was evidence of a genetic predisposition for peritonitis found in 2 studies, and for EPS in 1 study. Survival was found to be associated with a polymorphism in vascular endothelial growth factor and technique failure was associated with a polymorphism in the IL-1 receptor antagonist.

Conclusions:

There is evidence that characteristics of the peritoneal membrane and clinical outcomes for PD patients have genetic determinants. The most consistent association was between IL-6 gene polymorphisms and peritoneal membrane solute transport.  相似文献   

17.
BackgroundHaptoglobin (HP), which scavenges free, cell-toxic hemoglobin and has anti-inflammatory and immune-modulatory function in extravascular tissues, may represent an excellent candidate gene to investigate the life-span expectancy.MethodsHP 1/2 polymorphism has been determined for 1072 (569 females, 503 males) unrelated healthy individuals from Central Italy, 18–106 years old, divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes. HP*1F/S subtyping was also performed to check the possible existence for a preferential advantage of HP*1F or HP*1S allele.ResultsHP*1/*1 genotype results associated to increased probability of young subjects of attaining longevity (Comparison 1: O.R. 1.709, p = 0.0114) with a concomitant advantage of HP*1 allele (Comparison 1: O.R. 1.273, p = 0.0194). On the other side, carriers of HP*2 allele displayed an overall significant disadvantage in reaching Age Class 2 (O.R. 0.585, p = 0.0092). No significant differences were noticed between age groups either considering total HP*1F and HP*1S allele frequencies or according to HP 1/2 genotypes.ConclusionThe crucial role played by HP in aging process is warranted by its many established functions and its related phenotypes so that it may be considered an important gene involved in the determination of human survival.  相似文献   

18.
ObjectivesThe aim of this study was to estimate the serum activity of paraoxonase 1(PON1) and assess the distribution of PON1 polymorphisms in MS patients in the relapse phase.Design and methodsPON1 and arylesterase (ARE) serum activities were measured in two equal groups (each group 63 cases) of relapsing–remitting MS patients and healthy individuals.ResultsMean values for serum PON1 and ARE activities were 90.3 ± 63.4 and 182.1 ± 128.7 IU/L for patients and 99.9 ± 73.3 and 190.8 ± 150.3 IU/L for controls. Those values were not statistically significant (p = 0.242 and p = 0.378), respectively. Comparing genotype distributions and allele frequencies in both groups for PON1 Q192R and PON L55M polymorphisms did not show any statistical difference.ConclusionIn a selected group of MS patients in relapsing phase no statistically significant difference in PON1 and ARE activities was detected but the mean values for the serum enzyme activities were lower in MS patients.  相似文献   

19.
20.
ObjectiveThe purpose of this study was to compare pulmonary function and respiratory muscle strength and endurance in individuals with thoracic outlet syndrome (TOS) and healthy participants.MethodsSixty-two individuals with TOS (mean age 30.81 ± 10.69 years; 10 male, 52 female) and 47 healthy individuals (mean age 30.64 ± 9.16 years; 14 male, 33 female) participated in this study. Pulmonary function testing was performed using a spirometer. Respiratory muscle strength (maximal inspiratory pressure [MIP] and maximal expiratory pressure [MEP]) were measured using a mouth pressure device. Respiratory muscle endurance was tested at 35% MIP and measured as the time in seconds from the start of the test to voluntary exhaustion.ResultsAge distribution and physical characteristics were similar between the groups (P > .05). All pulmonary function parameters except for peak expiratory flow rate were similar in patients with TOS and healthy controls (P > .05). Patients with TOS had significantly lower peak expiratory flow rate, MIP, MIP%, MEP, MEP%, and respiratory muscle endurance compared with controls (P < .05). Forty-six patients with TOS (74.2%) had MIP values below the lower limit of the 95% CI of the control group (97.05-113.88 cmH2O), and 53 patients with TOS (85.2%) had MEP values below the lower limit of the 95% CI of the control group (124.74-146.49 cmH2O).ConclusionExpiratory flow rate and respiratory muscle strength and endurance may be adversely affected in TOS. Trunk muscles perform both postural and breathing functions. Therefore, disruption in one function may negatively affect the other.  相似文献   

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