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1.
Jie Zhang Jing He Xiao-Hong Zeng Shi-Jun Ge Yu Huang Jie Su Xue-Mei Ding Ji-Qing Yang Yong-Jiu Cao Hong Chen Ying-Hong Zhang Bao-Sheng Zhu 《PloS one》2015,10(4)
Objectives
The aim of this study was to investigate the geographic distribution of β-globin gene mutations in different ethnic groups in Yunnan province.Methods
From 2004 to 2014, 1,441 subjects with hemoglobin disorders, identified by PCR-reverse dot blot and DNA sequencing, were studied according to ethnicity and geographic origin. Haplotypes were examined among 41 unrelated thalassemia chromosomes.Results
Eighteen β-thalassemia mutations and seven hemoglobin variants were identified for 1,616 alleles in 22 different ethnic groups from all 16 prefecture-level divisions of Yunnan. The prevalence of β-thalassemia was heterogeneous and regionally specific. CD 41-42 (-TCTT) was the most prevalent mutation in the populations of northeastern Yunnan. CD 17 (A>T) was the most common mutation in the populations of southeastern Yunnan, especially for the Zhuang minority, whereas Hb E (CD 26, G>A) was the most prevalent mutation in populations of southwestern Yunnan, especially for the Dai minority. Among the seven types of haplotypes identified, CD 17 (A>T) was mainly linked to haplotype VII (+ - - - - - +) and IVS-II-654 (C>T) was only linked to haplotype I (+ - - - - + +).Conclusion
Our data underline the heterogeneity of β-globin gene mutations in Yunnan. This distribution of β-globin mutations in the geographic regions and ethnic populations provided a detailed ethnic basis and evolutionary view of humans in southern China, which will be beneficial for genetic counseling and prevention strategies. 相似文献2.
Xudong Sun Yuanyuan Xu Li Wang Fuhua Zhang Jinhua Zhang Ximei Fu Tao Jing Jian Han 《PloS one》2016,11(1)
Background
Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection.Methods
Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI).Results
A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup.Conclusion
Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results. 相似文献3.
Xianmin Meng Kang Yin Jiangrong Wang Ping Dong Li Liu Yinzhong Shen Li Shen Qing Ma Hongzhou Lu Weimin Cai 《PloS one》2015,10(6)
Objectives
The main aim of this study was to investigate the effect of CYP2B6 gene polymorphisms on efavirenz (EFV) plasma concentrations in Han Chinese patients with human immunodeficiency virus (HIV) infection.Methods
In total, 322 patients were recruited for study. EFV plasma concentrations at steady-state were determined using high-performance liquid chromatography. Genotyping for seven single nucleotide polymorphisms (SNPs), including 171+967C>A, 171+3212C>T, 171+4335T>C, 516G>T, 785A>G, 1295-913G>A, and *1355A>G of CYP2B6, was performed using ligase detection reaction (LDR). SPSS 18.0 and Haploview 4.2 were applied for statistical analyses.Results
The average EFV concentration of patients was 2.35±2.09 μg/mL. Overall, 22% patients displayed EFV concentrations out of the therapeutic range of 1–4 μg/mL (13.1% < 1 μg/mL, 9.3% > 4 μg/mL). We observed significant association of 171+967C>A, 171+4335T>C, 516G>T, 785A>G and *1355A>G with high plasma EFV levels (p<.01). The predictive accuracy values of 171+4335CC, 516TT and 785GG for EFV concentrations > 4 μg/mL were 56.7%, 56.7% and 60%, respectively. We observed strong linkage disequilibrium for 171+967C>A, 171+4335T>C, 516G>T and 785A>G, resulting in five haplotypes. The frequencies of the five haplotypes (high to low) were as follows: CCTG (0.328), ACTG (0.280), ACCT (0.189), ATTG (0.186) and ACCG (0.017). The frequency of CCTG (0.524) in patients with EFV plasma concentrations < 1 μg/mL was significantly higher than that in other patient groups, while that of ACCT (0.733) was significantly higher in patients with EFV concentrations > 4 μg/mL, relative to other patient groups. Average EFV concentrations of patients carrying ACTG (1.78 μg/mL), ACCT (7.50 μg/mL), and ATTG (1.92 μg/mL) haplotypes were markedly higher than those of patients carrying the CCTG haplotype. The predictive accuracy of ACCT for EFV > 4 μg/mL was 81%.Conclusions
Chinese patients administered standard doses of EFV require therapeutic drug monitoring or personalized medication management. Based on the current findings, we propose that 171+4335T>C, 516G>T, 785A>G and haplotype ACCT may be effectively used as genomic markers for EFV, which should aid in improving the efficacy of EFV-containing treatments and reduce the incidence of adverse reactions. 相似文献4.
Background
Oculocutaneous albinism (OCA) is an autosomal recessive disorder. The most common type OCA1 and OCA2 are caused by homozygous or compound heterozygous mutations in the tyrosinase gene (TYR) and OCA2 gene, respectively.Objective
The purpose of this study was to evaluate the molecular basis of oculocutaneous albinism in four Chinese families.Patients and Methods
Four non-consanguineous OCA families were included in the study. The TYR and OCA2 genes of all individuals were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database.Results
Four patients with a diagnosis of oculocutaneous albinism, presented with milky skin, white or light brown hair and nystagmus. Genetic analyses demonstrated that patient A was compound heterozygous for c.1037-7T.A, c.1037-10_11delTT and c.1114delG mutations in the TYR gene; patient B was heterozygous for c.593C>T and c.1426A>G mutations in the OCA2 gene, patients C and D were compound heterozygous mutations in the TYR gene (c.549_550delGT and c.896G>A, c.832C>T and c.985T>C, respectively). The heterozygous c.549_550delGT and c.1114delG alleles in the TYR gene were two novel mutations. Interestingly, heterozygous members in these pedigrees who carried c.1114delG mutations in the TYR gene or c.1426A>G mutations in the OCA2 gene presented with blond or brown hair and pale skin, but no ocular disorders when they were born; the skin of these patients accumulated pigment over time and with sun exposure.Conclusion
This study expands the mutation spectrum of oculocutaneous albinism. It is the first time, to the best of our knowledge, to report that c.549_550delGT and c.1114delG mutations in the TYR gene were associated with OCA. The two mutations (c.1114delG in the TYR gene and c.1426A>G in the OCA2 gene) may be responsible for partial clinical manifestations of OCA. 相似文献5.
Elisa Rossi Daniela Basso Carlo-Federico Zambon Filippo Navaglia Eliana Greco Michela Pelloso Serena Artuso Andrea Padoan Matilde Pescarin Ada Aita Dania Bozzato Stefania Moz Mara Cananzi Graziella Guariso Mario Plebani 《PloS one》2015,10(4)
Background
TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner.Methods
511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence).Results
Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations.Conclusion
TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk. 相似文献6.
Qi Peng Siping Li Keze Ma Wenrui Li Qiang Ma Xiaoguang He Yuejing He Ting He Xiaomei Lu 《PloS one》2015,10(3)
Background
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymatic disorder of the erythrocytes that affects 400 million people worldwide. We developed a PCR-reverse dot blot (RDB) assay to screen twenty genotypes of seventeen Chinese G6PD mutations and investigate the spectrum of G6PD deficiency mutations in Dongguan District, Guangdong Province, in southern China.Method
The PCR-RDB assay consists of multiplex PCR amplification of seven fragments in the G6PD target sequence of wild-type and mutant genomic DNA samples followed by hybridization to a test strip containing allele-specific oligonucleotide probes. A total of 16,464 individuals were analyzed by a combination of phenotypic screening and genotypic detection using the PCR-RDB assay and DNA sequence analysis.Results
The PCR-RDB assay had a detection rate of 98.1%, which was validated by direct sequencing in a blind study with 100% concordance. The G6PD deficiency incidence rate in Dongguan District is 4.08%. Thirty-two genotypes from 469 individuals were found. The two most common variants were c.1376G>T and c.1388G>A, followed by c.95A>G, c.871G>A, c.392G>T, and c.1024 C>T. In addition, two rare mutations (c.703C>A and c.406C>T) were detected by DNA sequencing analysis. In our study, 65 cases harbored the C1311T/IVS polymorphism and 67 cases were homozygote.Conclusion
The PCR-RDB assay we established is a reliable and effective method for screening G6PD mutations in the Chinese population. Data on the spectrum of mutations in the Dongguan District is beneficial to the clinical diagnosis and prevention of G6PD deficiency. 相似文献7.
Shubhashree Uppangala Shilly Dhiman Sujit Raj Salian Vikram Jeet Singh Guruprasad Kalthur Satish Kumar Adiga 《PloS one》2015,10(3)
Background
Concerns regarding the safety of ICSI have been intensified recently due to increased risk of birth defects in ICSI born children. Although fertilization rate is significantly higher in ICSI cycles, studies have failed to demonstrate the benefits of ICSI in improving the pregnancy rate. Poor technical skill, and suboptimal in vitro conditions may account for the ICSI results however, there is no report on the effects of oocyte manipulations on the ICSI outcome.Objective
The present study elucidates the influence of mock ICSI on the functional and genetic integrity of the mouse oocytes.Methods
Reactive Oxygen Species (ROS) level, mitochondrial status, and phosphorylation of H2AX were assessed in the in vivo matured and IVM oocytes subjected to mock ICSI.Results
A significant increase in ROS level was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P<0.05-0.001) whereas unique mitochondrial distribution pattern was found only in IVM oocytes (P<0.01-0.001). Importantly, differential H2AX phosphorylation was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P <0.001).Conclusion
The data from this study suggests that mock ICSI can alter genetic and functional integrity in oocytes and IVM oocytes are more vulnerable to mock ICSI induced changes. 相似文献8.
Isabel De Castro-Orós Rosa Solà Rosa María Valls Angel Brea Pilar Mozas Jose Puzo Miguel Pocoví 《PloS one》2016,11(3)
Background
Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial NCT01562080, there was large interindividual variability in the plasma LDLc response to AP supplementation. We hypothesized that the variability in LDLc response to AP supplementation may be linked to LDLR and PCSK9 polymorphisms.Material and Methods
We sequenced the LDLR 3′ and 5′ untranslated regions (UTR) and the PCSK9 5′ UTR of 102 participants with moderate hypercholesterolemia in trial NCT01562080. In this trial, 50 individuals were treated with AP supplementation and the rest with placebo.Results
Multiple linear regression analysis, using the response of LDLc levels to AP as the dependent variable, revealed that polymorphisms rs2149041 (c.-3383C>G) in the PCSK9 5′ UTR and rs14158 (c.*52G>A) in the LDLR 3′ UTR explained 14.1% and 6.4%, respectively, of the variability after adjusting for gender, age, and BMI of individuals. Combining polymorphisms rs2149041 and rs14158 explained 20.5% of this variability (p < 0.004).Conclusions
Three polymorphisms in the 3′ UTR region of LDLR, c.*52G>A, c.*504G>A, and c.*773A>G, and two at the 5′ UTR region of PCSK9, c.−3383C>G and c.−2063A>G, were associated with response to AP. These results could explain the variability observed in the response to berberine among people with moderate hypercholesterolemia, and they may be useful in identifying patients who could potentially benefit from supplementation with AP. 相似文献9.
Purpose
This study aimed to investigate the relationship between neuroticism, hopelessness, and depression among older Korean immigrants. To extend this line of research, this study aimed to examine the effects of neuroticism and hopelessness in predicting depression among older Korean immigrants.Methods
Data for this study came from a survey of 220 first generation Korean immigrants aged 65 years or older in Los Angeles County in 2012. Data were collected by face-to-face interviews with trained social workers using a structured questionnaire translated into Korean. All interviews were conducted in Korean. The neuroticism sub-scale of the Eysenck Personality Questionnaire was used to assess neuroticism (EPQN). Hopelessness was measured by the Beck Hopelessness Scale (BHS). Depression was measured by the 20-item Center of Epidemiological Studies Depression (CES-D) scale.Results
The study found that age (β = .26, p< .01), gender (β = -.13, p< .01), income (β = -.13, p< .01), neuroticism (β = .51, p< .01), and hopelessness (β = .15, p< .01) were significant predictors of depression.Conclusion
The study provides preventive strategies that would help in the development of depression-reduction services or programs for the population, especially for those living with neuroticism and hopelessness. 相似文献10.
Shanthi Duraimani Robert H. Schneider Otelio S. Randall Sanford I. Nidich Shichen Xu Muluemebet Ketete Maxwell A. Rainforth Carolyn Gaylord-King John W. Salerno John Fagan 《PloS one》2015,10(11)
Background
African Americans suffer from disproportionately high rates of hypertension and cardiovascular disease. Psychosocial stress, lifestyle and telomere dysfunction contribute to the pathogenesis of hypertension and cardiovascular disease. This study evaluated effects of stress reduction and lifestyle modification on blood pressure, telomerase gene expression and lifestyle factors in African Americans.Methods
Forty-eight African American men and women with stage I hypertension who participated in a larger randomized controlled trial volunteered for this substudy. These subjects participated in either stress reduction with the Transcendental Meditation technique and a basic health education course (SR) or an extensive health education program (EHE) for 16 weeks. Primary outcomes were telomerase gene expression (hTERT and hTR) and clinic blood pressure. Secondary outcomes included lifestyle-related factors. Data were analyzed for within-group and between-group changes.Results
Both groups showed increases in the two measures of telomerase gene expression, hTR mRNA levels (SR: p< 0.001; EHE: p< 0.001) and hTERT mRNA levels (SR: p = 0.055; EHE: p< 0.002). However, no statistically significant between-group changes were observed. Both groups showed reductions in systolic BP. Adjusted changes were SR = -5.7 mm Hg, p< 0.01; EHE = -9.0 mm Hg, p < 0.001 with no statistically significant difference between group difference. There was a significant reduction in diastolic BP in the EHE group (-5.3 mm Hg, p< 0.001) but not in SR (-1.2 mm Hg, p = 0.42); the between-group difference was significant (p = 0.04). The EHE group showed a greater number of changes in lifestyle behaviors.Conclusion
In this pilot trial, both stress reduction (Transcendental Meditation technique plus health education) and extensive health education groups demonstrated increased telomerase gene expression and reduced BP. The association between increased telomerase gene expression and reduced BP observed in this high-risk population suggest hypotheses that telomerase gene expression may either be a biomarker for reduced BP or a mechanism by which stress reduction and lifestyle modification reduces BP.Trial Registration
ClinicalTrials.gov NCT00681200 相似文献11.
Florent Besnier Victorine Lenclume Patrick Gérardin Adrian Fianu Jérémy Martinez Nadège Naty Sylvaine Porcherat Karim Boussaid Stéphane Schneebeli Eric Jarlet Sarah Hatia Georges Dalleau Chantal Verkindt Jean-Frédéric Brun Marie-Paule Gonthier Fran?ois Favier 《PloS one》2015,10(11)
Objectives
Lifestyle combined interventions are a key strategy for preventing type-2 diabetes (T2DM) in overweight or obese subjects. In this framework, LIPOXmax individualized training, based on maximal fat oxidation [MFO], may be a promising intervention to promote fat mass (FM) reduction and prevent T2DM. Our primary objective was to compare three training programs of physical activity combined with a fruit- and vegetable-rich diet in reducing FM in overweight or obese women.Design and setting
A five months non-blinded randomized controlled trial (RCT) with three parallel groups in La Réunion Island, a region where metabolic diseases are highly prevalent.Subjects
One hundred and thirty-six non-diabetic obese (body mass index [BMI]: 27–40 kg/m2) young women (aged 20–40) were randomized (G1: MFO intensity; G2: 60% of VO2-peak intensity; G3: free moderate-intensity at-home exercise following good physical practices).Outcomes
Anthropometry (BMI, bodyweight, FM, fat-free mass), glucose (fasting plasma glucose, insulin, HOMA-IR) and lipid (cholesterol and triglycerides) profiles, and MFO values were measured at month-0, month-3 and month-5.Results
At month-5, among 109 women assessed on body composition, the three groups exhibited a significant FM reduction over time (G1: -4.1±0.54 kg; G2: -4.7±0.53 kg; G3: -3.5±0.78 kg, p<0.001, respectively) without inter-group differences (p = 0.135). All groups exhibited significant reductions in insulin levels or HOMA-IR index, and higher MFO values over time (p<0.001, respectively) but glucose control improvement was higher in G1 than in G3 while MFO values were higher in G1 than in G2 and G3. Changes in other outcome measures and inter-group differences were not significant.Conclusion
In our RCT the LIPOXmax intervention did not show a superiority in reducing FM in overweight or obese women but is associated with higher MFO and better glucose control improvements. Other studies are required before proposing LIPOXmax training for the prevention of T2DM in overweight or obese women.Trial Registration
ClincialTrials.gov NCT01464073 相似文献12.
Caiyun Zhang Chao Li Minhui Zhu Qingzhou Zhang Zhenghua Xie Gang Niu Xicheng Song Lei Jin Guojun Li Hongliang Zheng 《PloS one》2013,8(4)
Background
The 1306 C>T, 1171 5A>6A, and 1562C>T polymorphisms of matrix metalloproteinase (MMP) 2, MMP3, and MMP9 genes, respectively, have been found to be functional and may contribute to head and neck carcinogenesis. However, the results of case-control studies examining associations between MMP polymorphisms and head and neck cancer (HNC) risk remain inconclusive. Therefore, we performed a meta-analysis to further evaluate the role of these polymorphisms in HNC development.Methods
We searched PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar to identify all published case-control studies of MMP2-1306 C>T, MMP3-1171 5A>6A, and MMP9-1562 C>T polymorphisms and HNC risk in the meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between these polymorphisms and HNC risk.Results
Thirteen studies were included in this meta-analysis. For MMP2-1306 C>T polymorphism, significant associations were observed under three genetic models both in overall comparison and in a hospital-based subgroup, and in oral cavity cancer and nasopharyngeal cancer under dominant model as well. For MMP3-1171 5A>6A and MMP9-1562 C>T polymorphisms, no association was found in overall comparison; however, in subgroup analyses based on ethnicity and tumor site, significant associations were detected between the MMP3-1171 5A>6A polymorphism and HNC risk in a European population and pharyngeal/laryngeal cancer under two genetic contrasts.Conclusion
This meta-analysis suggests that the MMP2-1306 C>T polymorphism is associated with HNC risk, as is the MMP3-1171 5A>6A polymorphism specifically in some subgroups. Further studies with larger sample sizes are warranted. 相似文献13.
Objectives
To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL)-1β genes and occupational dust exposure on the risk of silicosis.Methods
We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE) for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1β genes. We estimated odds ratios(ORs), 95% confidence intervals(95%CIs), and p-values using logistic regression models adjusted for selected confounders.Results
After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12–5.12] and 3.62 [1.63–8.02], respectively). Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C in Nalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24[0.06–0.88]). Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04–6.12] and 5.19[1.88–14.35], respectively). Among subjects with CDE greater than 120 mg/m3×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35–207.39] and 3.47[1.40–8.64], respectively).Conclusions
Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status. 相似文献14.
S. Justin Carlus Saumya Sarkar Sandeep Kumar Bansal Vertika Singh Kiran Singh Rajesh Kumar Jha Nirmala Sadasivam Sri Revathy Sadasivam P. S. Gireesha Kumarasamy Thangaraj Singh Rajender 《PloS one》2016,11(3)
Background
Optimum efficiency of the folate pathway is considered essential for adequate ovarian function. 677 C>T substitution in the 5, 10-methylene tertrahydrofolatereductase (MTHFR) gene compromises activity of the MTHFR enzyme by about 50%. The significance of correlation between 677C>T substitution and PCOS remains dubious due to the low power of published studies.Methods and Results
We analyzed MTHFR 677 C>T site in ethnically two different PCOS case-control groups (total 261 cases and 256 controls) from India. The data analysis revealed a lack of association between this polymorphism and PCOS [OR = 1.11 (95%CI = 0.71–1.72), P = 0.66]. Group-wise analysis on the basis of ethnicity also revealed no association in any of the ethnic groups [Indo-Europeans, P = 1; Dravidians, P = 0.70]. Homocysteine levels did not differ significantly between cases (15.51 μmol/L, SD = 2.89) and controls (15.89 μmol/L, SD = 2.23). We also undertook a meta-analysis on 960 cases and 1028 controls, which suggested a significant association of the substitution with PCOS in the dominant model of analysis (OR = 1.47 (95%CI = 1.04–2.09), P = 0.032]. Trial sequential analysis corroborated findings of the traditional meta-analysis. However, we found that the conclusions of meta-analysis were strongly influenced by studies that deviated from the Hardy Weinberg equilibrium. A careful investigation of each study and a trial sequential analysis suggested that 677 C>T substitution holds no clinical significance in PCOS in most of the populations.Conclusion
In conclusion, MTHFR 677 C>T polymorphism does not affect PCOS risk in India. The association seen in the meta-analysis is due to an outlier study and studies showing deviation from the Hardy Weinberg equilibrium. 相似文献15.
Hong Guo Fengyu Sun Lihang Dong Huiying Chang Xingbo Gu Haiyu Zhang Lijiang Sheng Ye Tian 《PloS one》2015,10(10)
Objective
We investigated the association of ankle-brachial blood pressure index (ABI), interarm blood pressure (BP) difference and interankle BP difference, obtained by simultaneous four-limb BP measurement, with history of stroke in a Chinese adult population.Methods
This cross-sectional study included 1485 participants aged ≥35 years in the framework of the China Hypertension Survey. We performed simultaneous four-limb BP measurement using oscillometric devices with the participants in the supine position and calculated ABI and interarm/interankle BP differences between the 4 limbs. Logistic regression analysis was used to estimate the association of these BP parameters and other factors with a history of stroke.Results
In univariate analyses, participants with ABI <0.9, interarm BP difference ≥15 mmHg, and interankle BP difference ≥10 mmHg had a higher prevalence of stroke than those without (p < 0.0001, p = 0.0152, p = 0.002, respectively). Multiple logistic regression analyses suggested, ABI <0.9 was independently associated with a history of stroke after adjustment for interarm BP difference ≥15 mmHg, interankle BP difference ≥10 mmHg, and traditional risk factors for stroke (p = 0.001). An interankle BP difference ≥10 mmHg was associated with prior stroke after the two variables of hypertension and ABI were removed from the logistic regression model (p = 0.0142). Net reclassification improvement analysis showed that inclusion of interankle BP difference ≥10 mmHg to the independent risk factors (age, family history of stroke, hypertension, and ABI) improved net reclassification by 11.92%.Conclusion
ABI <0.9 is an independent risk factor for stroke prevalence in Chinese adults and it just detected a small propotion of paticipants. The addition of interankle BP difference ≥10 mmHg to the independent risk factors for stroke may improve the prediction of stroke. 相似文献16.
Objectives
To investigate the role of Cryptococcus in the immune system of immunocompetent patients with pulmonary cryptococcosis (PC) by analysing the dynamic changes of patients’ immune status before and after antifungal therapy.Methods
The level of the serum interferon-γ (IFN-γ) and interleukin (IL)-2, -4, -10 and -12 was measured before and after 6-months of treatment. Peripheral blood samples were obtained from 30 immunocompetent PC patients and 30 age- and gender-matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and incubated with recombinant human IL-12 (rhIL-12) for 48 h. Then the concentrations of IFN-γ and IL-4 in the supernatant were analysed.Results
Baseline serum IFN-γ level was significantly lower in the PC patients as compared with the control group (P < 0.001). The serum IL-2 and IFN-γ of PC patients were significantly increased after appropriate treatments (P < 0.05 and P < 0.001 when compared to their baseline levels). The productions of IFN-γ in the culture supernatant of PBMCs showed no significant difference between the control and PC patients both before and after antifungal treatments. RhIL-12 is a potent stimulus for IFN-γ production. Culture PBMCs collected from PC patients before treatments had a smaller increase of IFN-γ production in the present of rhIL-12 than the control (P < 0.01); PBMCs from PC patients completing 6-months of treatment showed a comparable increase of IFN-γ production by rhIL-12 stimulation to the control group.Conclusions
In apparently immunocompetent patients with PC, a normalization of serum IFN-γ was achieved after recovery from infection. This suggests that Cryptococcus infection per se can suppress the immune system and its elimination contributes to the reestablishment of an immune equilibrium. 相似文献17.
18.
Fazhong He Jianquan Luo Zhiying Luo Lan Fan Yijing He Dingliang Zhu Jinping Gao Sheng Deng Yan Wang Yuesheng Qian Honghao Zhou Xiaoping Chen Wei Zhang 《PloS one》2013,8(4)
Background
KCNH2 (hERG) potassium channels have an integral role in regulating the excitability of smooth muscle cells. Some pathways driven by angiotensin II, nitric oxide and adrenergic receptors blocker are involved in modulating the properties of KCNH2 potassium channels. And these pathways are closely related to blood pressure regulation. Therefore, we hypothesized that KCNH2 genetic polymorphisms may affect blood pressure response to the antihypertensive drug therapies.Materials and Methods
To evaluate the interactions between KCNH2 genetic polymorphisms and individual blood pressure response to antihypertensive drugs, 370 subjects with essential hypertension (EH) were studied. In evaluating the interactions between KCNH2 genetic polymorphisms and drug response to blood pressure, multivariable ANOVA analysis followed by Bonferroni correction were carried out.Results
There were statistically significant interactions between KCNH2 (1956, C>T) polymorphism and DBP change (P = 0.010), MAP change (P = 0.014) on azelnidipine or nitrendipine therapy patients at the end of 6 weeks. We found that the KCNH2 (1956,C>T) polymorphism was associated with the hypotensive effects of α,β-ADR blockers of DBP change at the end of 4 and 6 weeks'' treatment in an age- and gender-dependent manner (P = 0.007 and 0.019, respectively). Similar results were also observed for changes in MAP at the end of 4 and 6 weeks (P-values were 0.035 and 0.078, respectively). While patients who received imidapril, candesartan and irbesartan therapy, no significant difference in drug response among KCNH2(1956,C>T) genotype was observed.Conclusion
We have reported for the first time that KCNH2 (1956, C>T) polymorphism is associated with efficacy of antihypertensive drugs CCBs and ADR blockers, and may serve as a novel biomarker for individualized therapy for certain antihypertensive drugs. 相似文献19.
Gabriela Avila-Pedretti Jesús Tornero Antonio Fernández-Nebro Francisco Blanco Isidoro González-Alvaro Juan D. Ca?ete Joan Maymó Mercedes Alperiz Benjamín Fernández-Gutiérrez Alex Olivé Héctor Corominas Alba Erra Adrià Aterido María López Lasanta Raül Tortosa Antonio Julià Sara Marsal 《PloS one》2015,10(4)
Objective
Anti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25–30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response.Methods
A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy.Results
We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a significant association between the genetic variation at DHX32 (rs12356233, corrected P=0.019) and a nominally significant association between RGS12 and the response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive group of patients, we also found a nominally significant association between RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042).Conclusions
In the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA. 相似文献20.
Radia Boudjenah Denise Molina-Gomes Antoine Torre Florence Boitrelle Stéphane Taieb Esther Dos Santos Robert Wainer Philippe de Mazancourt Jacqueline Selva Fran?ois Vialard 《PloS one》2014,9(9)