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1.
Nathella Pavan Kumar Rathinam Sridhar Luke E. Hanna Vaithilingam V. Banurekha Thomas B. Nutman Subash Babu 《PloS one》2014,9(10)
Background
Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.Aims/Methodology
To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.Results
We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.Conclusions
Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets. 相似文献2.
Tineke van de Weijer Lauren Marie Sparks Esther Phielix Ruth Carla Meex Noud Antonius van Herpen Matthijs Karel C. Hesselink Patrick Schrauwen Vera Bettina Schrauwen-Hinderling 《PloS one》2013,8(2)
Introduction
Mitochondrial dysfunction, lipid accumulation, insulin resistance and metabolic inflexibility have been implicated in the etiology of type 2 diabetes (T2D), yet their interrelationship remains speculative. We investigated these interrelationships in a group of T2D and obese normoglycemic control subjects.Methods
49 non-insulin dependent male T2D patients and 54 male control subjects were enrolled, and a hyperinsulinemic-euglycemic clamp and indirect calorimetry were performed. A muscle biopsy was taken and intramyocellular lipid (IMCL) was measured. In vivo mitochondrial function was measured by PCr recovery in 30 T2D patients and 31 control subjects.Results
Fasting NEFA levels were significantly elevated in T2D patients compared with controls, but IMCL was not different. Mitochondrial function in T2D patients was compromised by 12.5% (p<0.01). Whole body glucose disposal (WGD) was higher at baseline and lower after insulin stimulation. Metabolic flexibility (ΔRER) was lower in the type 2 diabetic patients (0.050±0.033 vs. 0.093±0.050, p<0.01). Mitochondrial function was the sole predictor of basal respiratory exchange ratio (RER) (R2 = 0.18, p<0.05); whereas WGD predicted both insulin-stimulated RER (R2 = 0.29, p<0.001) and metabolic flexibility (R2 = 0.40, p<0.001).Conclusions
These results indicate that defects in skeletal muscle in vivo mitochondrial function in type 2 diabetic patients are only reflected in basal substrate oxidation and highlight the importance of glucose disposal rate as a determinant of substrate utilization in response to insulin. 相似文献3.
Background
The blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-γ-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results.Aim
To investigate this new biomarker for active TB and LTBI in paediatrics.Method
We measured IP-10 levels using ELISA in supernatants of whole blood samples stimulated with TB-specific-antigens and negative control antigen.Results
IP-10 is produced in high levels following mycobacterial antigen stimulation in active TB (n = 17) and LTBI (n = 16) compared to controls (n = 16) and to IFN-γ. The baseline levels of IP-10 are increased in active TB and in LTBI, but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI.Conclusions
IP-10 is a biomarker for tuberculosis in children. However like IFNγ, IP-10 also does not distinguish between active TB and LTBI. 相似文献4.
Objective
To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC) patients.Methods
Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters.Results
A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08–25.6, P = 0.040). Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47–0.89, P = 0.007, random-effect).Conclusions
SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients. 相似文献5.
6.
Xiao Wang Jan Sundquist Bengt Z?ller Ashfaque A. Memon Karolina Palmér Kristina Sundquist Louise Bennet 《PloS one》2014,9(1)
Background
Recent reports suggest that immigrants from Middle Eastern countries are a high-risk group for type 2 diabetes (T2D) compared with Swedes, and that the pathogenesis of T2D may be ethnicity-specific. Deregulation of microRNA (miRNA) expression has been demonstrated to be associated with T2D but ethnic differences in miRNA have not been investigated. The aim of this study was to explore the ethnic specific expression (Swedish and Iraqi) of a panel of 14 previously identified miRNAs in patients without T2D (including those with prediabetes) and T2D.Methods
A total of 152 individuals were included in the study (84 Iraqis and 68 Swedes). Nineteen Iraqis and 14 Swedes were diagnosed with T2D. Expression of the 14 selected miRNAs (miR-15a, miR-20, miR-21, miR-24, miR-29b, miR-126, miR-144, miR-150, miR-197, miR-223, miR-191, miR-320a, miR-486-5p, and miR-28-3p) in plasma samples was measured by real-time PCR.Results
In the whole study population, the expression of miR-24 and miR-29b was significantly different between T2D patients and controls after adjustment for age, sex, waist circumference, family history of T2D, and a sedentary lifestyle. Interestingly, when stratifying the study population according to country of birth, we found that higher expression of miR-144 was significantly associated with T2D in Swedes (OR = 2.43, p = 0.035), but not in Iraqis (OR = 0.54, p = 0.169). The interaction test was significant (p = 0.017).Conclusion
This study suggests that the association between plasma miR-144 expression and T2D differs between Swedes and Iraqis. 相似文献7.
Robert S. Wallis Rodney Dawson Sven O. Friedrich Amour Venter Darcy Paige Tong Zhu Annette Silvia Jason Gobey Craig Ellery Yao Zhang Kathleen Eisenach Paul Miller Andreas H. Diacon 《PloS one》2014,9(4)
Rationale
Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients.Methods
Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25), or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA) were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv.Results
All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI) for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy''s criteria for serious liver injury.Conclusions
The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted.Trial Registration
ClinicalTrials.gov NCT01225640相似文献8.
Jenneke Leentjens Jessica Quintin Jelle Gerretsen Matthijs Kox Peter Pickkers Mihai G. Netea 《PloS one》2014,9(9)
Rationale
To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use.Methods
We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10) or the control group (n = 5). Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity.Results
β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan.Conclusion
The present study does not support the use of oral β-glucan to enhance innate immune responses in humans.Trial Registration
ClinicalTrials.gov NCT01727895相似文献9.
Objective
Identify and analyze the factors associated to length of hospital stay among HIV positive and HIV negative patients with tuberculosis in Manaus city, state of Amazonas, Brazil, in 2010.Methods
Epidemiological study with primary data obtained from monitoring of hospitalized patients with tuberculosis in Manaus. Data were collected by interviewing patients and analyzing medical records, according to the following study variables age, sex, co-morbidities, education, race, income, lifestyle, history of previous treatment or hospitalization due to tuberculosis, treatment regimen, adverse reactions, smear test, clinical form, type of discharge, and length of hospital stay. The associated factors were identified through chi-square or t-Student test at a 5% significance level.Results
Income from 1 to 3 minimum wages (P = 0.028), pulmonary tuberculosis form (P = 0.011), negative smear test or no information in this regard (P = 0.014), initial 6-month treatment scheme (P = 0.029), and adverse drug reactions (P = 0.021) were associated to prolonged hospital stay in HIV positive patients.Conclusion
We found out that although there were no significant differences in the length of hospital stay in HIV positive patients, all factors significantly associated to prolonged hospital stay occurred in this group of patients. This finding corroborates other studies indicating the severity of tuberculosis in HIV patients, which may also contribute to lengthen their hospital stay. 相似文献10.
Nathella Pavan Kumar Rathinam Sridhar Vaithilingam V. Banurekha Dina Nair Mohideen S. Jawahar Thomas B. Nutman Subash Babu 《PloS one》2013,8(2)
Background
Th1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), although little is known about their role in extrapulmonary forms of tuberculosis (TB).Methods
To identify the role of Th1, Th17, and Th22 cells in multi-focal TB lymphadenitis (TBL), we examined mycobacteria–specific immune responses in the whole blood of individuals with PTB (n = 20) and compared them with those with TBL (n = 25).Results
Elevated frequencies of CD4+ T cells expressing IFN- γ, TNF-α, and IL-2 were present in individuals with TBL compared with those with PTB at baseline and in response to ESAT-6 and CFP-10. Similarly, increased frequencies of CD4+ T cells expressing IL-17A, IL-17F, and IFN-γ were also present in individuals with TBL at baseline and following ESAT-6 and CFP-10 stimulation although no significant difference in frequency of Th22 cells was observed. Finally, frequencies of Th1 (but not Th17) cells exhibited a significantly negative correlation with natural regulatory T cell frequencies at baseline.Conclusions
Multi-focal TB lymphadenitis is therefore characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity. 相似文献11.
Murali K. Ravoori Lin Han Sheela P. Singh Katherine Dixon Jyoti Duggal Ping Liu Rajesh Uthamanthil Sanjay Gupta Kenneth C. Wright Vikas Kundra 《PloS one》2013,8(6)
Purpose
To evaluate the importance of morphology in quantifying expression after in vivo gene transfer and to compare gene expression after intra-arterial (IA) and intra-tumoral (IT) delivery of adenovirus expressing a SSTR2-based reporter gene in a large animal tumor model.Materials and Methods
Tumor directed IA or IT delivery of adenovirus containing a human somatostatin receptor type 2A (Ad-CMV-HA-SSTR2A) gene chimera or control adenovirus (Ad-CMV-GFP) was performed in VX2 tumors growing in both rabbit thighs. Three days later, 111In-octreotide was administered intravenously after CT imaging using a clinical scanner. 111In-octreotide uptake in tumors was evaluated the following day using a clinical gamma-camera. Gene expression was normalized to tumor weight with and without necrosis. This procedure was repeated on nine additional rabbits to investigate longitudinal gene expression both 5 days and 2 weeks after adenovirus delivery. CT images were used to evaluate tumor morphology and excised tissue samples were analyzed to determine 111In-octreotide biodistribution ex vivo.Results
VX2 tumors infected with Ad-CMV-HA-SSTR2 had greater 111In-octreotide uptake than with control virus (P<0.05). Intra-arterial and intra-tumoral routes resulted in similar levels of gene expression. Longitudinally, expression appeared to wane at 2 weeks versus 5 days after delivery. Areas of necrosis did not demonstrate significant uptake ex vivo. Morphology identified areas of necrosis on contrast enhanced CT and upon excluding necrosis, in vivo biodistribution analysis resulted in greater percent injected dose per gram (P<0.01) and corresponded better with ex vivo biodistribution(r = 0.72, P<0.01, Coefficient of the x-variable = .72) at 2 weeks than without excluding necrosis (P<0.01).Conclusion
Tumor specificity and high transgene expression can be achieved in tumors via both tumor directed intra-arterial and intra-tumoral delivery in a large animal tumor model. Using clinical machines, morphologic imaging contributes to functional imaging for quantifying SSTR2-based reporter expression in vivo. 相似文献12.
Gathsaurie Neelika Malavige Chandima Jeewandara K. M. Luckmaal Alles Maryam Salimi Laksiri Gomes Achala Kamaladasa S. D. Jayaratne Graham Stuart Ogg 《PLoS neglected tropical diseases》2013,7(9)
Background
Elevated IL-10 has been shown to be associated with severe dengue infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI.Materials and methods
Ex vivo and cultured IFNγ ELISpot assays for dengue virus (DENV) NS3 protein and non dengue viral proteins were carried out in 26 patients with acute DI (16 with dengue haemorrhagic fever) and 12 healthy dengue seropositive individuals from Sri Lanka. DENV serotype specific (SS) responses were determined by using a panel of SS peptides.Results
Serum IL-10 level were significantly higher (p = 0.02) in those who did not have in vitro responses to DENV-SS peptides (mean 144.2 pg/ml) when compared to those who responded (mean 75.7 pg/ml). DENV-NS3 specific ex vivo IFNγ ELISpot responses were also significantly lower (p = 0.0001) in those who did not respond to DENV-SS peptides (mean 42 SFU/million PBMCs) when compared to those who responded to DENV-SS peptides (mean 1024 SFU/million PBMCs). Serum IL-10 levels correlated significantly (p = 0.03) and inversely (Spearmans R = −0.45) with ex vivo DENV-NS3 specific responses but not with ex vivo non DENV specific responses (Spearmans R = −014, p = 0.52). Blockage of IL-10 in vitro significantly increased (p = 0.04) the ex vivo IFNγ ELISpot DENV-NS3 specific responses but had no effect on responses to non DENV proteins.Conclusion
IL-10 appears to contribute to the pathogenesis of acute dengue infections by inhibiting DENV-specific T cell responses, which can be restored by blocking IL-10. 相似文献13.
Lisa G. M. van Baarsen Saskia Vosslamber Marianne Tijssen Josefien M. C. Baggen Laura F. van der Voort Joep Killestein Tineke C. T. M. van der Pouw Kraan Chris H. Polman Cornelis L. Verweij 《PloS one》2008,3(4)
Background
Multiple sclerosis (MS) is a heterogeneous disease. In order to understand the partial responsiveness to IFNß in Relapsing Remitting MS (RRMS) we studied the pharmacological effects of IFNß therapy.Methodology
Large scale gene expression profiling was performed on peripheral blood of 16 RRMS patients at baseline and one month after the start of IFNß therapy. Differential gene expression was analyzed by Significance Analysis of Microarrays. Subsequent expression analyses on specific genes were performed after three and six months of treatment. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated in vitro with IFNß. Genes of interest were measured and validated by quantitative realtime PCR. An independent group of 30 RRMS patients was used for validation.Principal Findings
Pharmacogenomics revealed a marked variation in the pharmacological response to IFNß between patients. A total of 126 genes were upregulated in a subset of patients whereas in other patients these genes were downregulated or unchanged after one month of IFNß therapy. Most interestingly, we observed that the extent of the pharmacological response correlates negatively with the baseline expression of a specific set of 15 IFN response genes (R = −0.7208; p = 0.0016). The negative correlation was maintained after three (R = −0.7363; p = 0.0027) and six (R = −0.8154; p = 0.0004) months of treatment, as determined by gene expression levels of the most significant correlating gene. Similar results were obtained in an independent group of patients (n = 30; R = −0.4719; p = 0.0085). Moreover, the ex vivo results could be confirmed by in vitro stimulation of purified PBMCs at baseline with IFNß indicating that differential responsiveness to IFNß is an intrinsic feature of peripheral blood cells at baseline.Conclusion
These data imply that the expression levels of IFN response genes in the peripheral blood of MS patients prior to treatment could serve a role as biomarker for the differential clinical response to IFNß. 相似文献14.
Márton Doleschall Julianna Anna Szabó Júlia Pázmándi ágnes Szilágyi Klára Koncz Henriette Farkas Miklós Tóth Péter Igaz Edit Gláz Zoltán Prohászka Márta Korbonits Károly Rácz George Füst Attila Patócs 《PloS one》2014,9(9)
Purpose
Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels.Methods
The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available.Results
The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects.Conclusions
The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution. 相似文献15.
16.
Iva Subhanova Lucie Muchova Martin Lenicek Hendrik J. Vreman Ondrej Luksan Kristyna Kubickova Miluse Kreidlova Tomas Zima Libor Vitek Petr Urbanek 《PloS one》2013,8(3)
Background and Aims
Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV.Methods
Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naïve patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy.Results
Compared to the controls, substantially increased BLVRA expression was detected in PBL (p<0.001) of therapeutically naïve HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95% CI 1.05–214.2; P = 0.046). HMOX1/2 expression did not have any effect on the treatment outcome.Conclusion
Our results suggest that patients with chronic HCV infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA overexpression is associated with non-responsiveness to standard antiviral therapy; whereas, HMOX1/2 does not seem to have any predictive potential. 相似文献17.
Renguang Pei Yunfeng Zhou Guoxiang Wang Heping Wang Xinyu Huang Xiaoxing Yan Xiaohua Yang 《PloS one》2014,9(12)
Objective
To appraise the immediate and long-term outcomes of bronchial arterial embolization for life-threatening hemoptysis secondary to tuberculosis.Methods
112 patients with life-threatening hemoptysis due to tuberculosis underwent bronchial artery embolization from January 2004 to February 2014. Life-threatening hemoptysis was defined as expectoration of at least 400 ml of blood in 24 hour. The median follow-up is 20 months, ranging from 2 to 52 months.Results
The hemoptysis control rate was 86.6% at 14 days, 84.8% at 30 days, 78.6% at 240 days, 75.9% at 360 days, respectively. None of these characteristics, including gender, age and tuberculosis status, was significantly associated with immediate control of bleeding. Patients with active tuberculosis had a significantly longer recurrence-free duration than did patients with inactive tuberculosis (P = 0.040), which was further confirmed by Cox regression hazards model (P = 0.046). There was no spinal cord complication or mortality related to bronchial artery embolization. The most common complication was transient chest pain.Conclusion
Bronchial arterial embolization is an effective and safe technique in the management of life-threatening hemoptysis secondary to tuberculosis. Active tuberculosis may be associated with a lower rate of recurrence of hemoptysis. 相似文献18.
Neus Pueyo Francisco J. Ortega Josep M. Mercader José M. Moreno-Navarrete Monica Sabater Sílvia Bonàs Patricia Botas Elías Delgado Wifredo Ricart María T. Martinez-Larrad Manuel Serrano-Ríos David Torrents José M. Fernández-Real 《PloS one》2013,8(4)
Context
Surfactant protein-D (SP-D) is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs) affecting SP-D with insulin resistance and type 2 diabetes (T2D).Research Design and Methods
We evaluated a common genetic variant located in the SP-D coding region (rs721917, Met31Thr) in a sample of T2D patients and non-diabetic controls (n = 2,711). In a subset of subjects (n = 1,062), this SNP was analyzed in association with circulating SP-D concentrations, insulin resistance, and T2D. This SNP and others were also screened in the publicly available Genome Wide Association (GWA) database of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC).Results
We found the significant association of rs721917 with circulating SP-D, parameters of insulin resistance and T2D. Indeed, G carriers showed decreased circulating SP-D (p = 0.004), decreased fasting glucose (p = 0.0002), glycated hemoglobin (p = 0.0005), and 33% (p = 0.002) lower prevalence of T2D, estimated under a dominant model, especially among women. Interestingly, these differences remained significant after controlling for origin, age, gender, and circulating SP-D. Moreover, this SNP and others within the SP-D genomic region (i.e. rs10887344) were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC.Conclusions
SP-D gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations. 相似文献19.
Ambika P. Ashraf Jessica A. Alvarez Tanja Dudenbostel David Calhoun Russell Griffin Xudong Wang Lynae J. Hanks Barbara A. Gower 《PloS one》2014,9(12)
Objective
The role of vitamin D in cardiovascular health remains debated as results have been inconsistent. Previous studies have not considered the bioavailability of 25-hydroxy vitamin D [25(OH)D]. Objectives of our study were to investigate the association between serum concentrations of total, free and bioavailable 25(OH)D and independent predictors of cardiovascular risk such as flow mediated dilatation (FMD) and augmentation index (AIx).Design
This cross-sectional study included 47 post-menarchal, adolescent females [31 African American (AA) and 16 European American (EA)].Methods
AIx was standardized to a heart rate of 75 beats/min (AIx75). Free and bioavailable 25(OH)D concentrations were calculated from standard formulas.Results and Conclusions
Mean age of the participants was 15.8±1.4 years and mean body mass index was 23.1±4.0 kg/m2. Serum total 25(OH)D was not associated with FMD, but was positively associated with AIx75 in the adjusted model (rho = 0.4, P = 0.03). AIx75 was positively associated with bioavailable 25(OH)D (rho = 0.4, P = 0.004) and free 25(OH)D (rho = 0.4, P = 0.009) and the associations persisted after adjusting for covariates. In race-specific analyses, total, free and bioavailable 25(OH)D were strongly positively associated with AIx75 in AA (rho = 0.5, 0.4, 0.4, respectively), which persisted even after adjusting for covariates. Whereas in EA there was an inverse association between total 25(OH)D and AIx75 in EA (rho = −0.6), which attenuated after adjusting for covariates.Conclusion
Circulating total, free and bioavailable 25(OH)D were associated with arterial stiffness in adolescent girls, and these associations were race dependent. Notwithstanding, the implications of associations between vascular function indices and 25(OH)D remains unclear. 相似文献20.