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1.
EBioMedicine ; 79: 104014, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35487057

RESUMO

BACKGROUND: Accumulative evidences have shown that dysregulation of biological pathways contributed to the initiation and progression of malignant tumours. Several methods for pathway activity measurement have been proposed, but they are restricted to making comparisons between groups or sensitive to experimental batch effects. METHODS: We introduced a novel method for individualized pathway activity measurement (IPAM) that is based on the ranking of gene expression levels in individual sample. Taking advantage of IPAM, we calculated the pathway activity of 318 pathways from KEGG database in the 10528 tumour/normal samples of 33 cancer types from TCGA to identify characteristic dysregulated pathways among different cancer types. FINDINGS: IPAM precisely quantified the level of activity of each pathway in pan-cancer analysis and exhibited better performance in cancer classification and prognosis prediction over five widely used tools. The average ROC-AUC of cancer diagnostic model using tumour-educated platelets (TEPs) reached 92.84%, suggesting the potential of our algorithm in early diagnosis of cancer. We identified several pathways significantly deregulated and associated with patient survival in a large fraction of cancer types, such as tyrosine metabolism, fatty acid degradation, cell cycle, p53 signalling pathway and DNA replication. We also confirmed the dominant role of metabolic pathways in cancer pathway dysregulation and identified the driving factors of specific pathway dysregulation, such as PPARA for branched-chain amino acid metabolism and NR1I2, NR1I3 for fatty acid metabolism. INTERPRETATION: Our study will provide novel clues for understanding the pathological mechanisms of cancer, ultimately paving the way for personalized medicine of cancer. FUNDING: A full list of funding can be found in the Acknowledgements section.

2.
Chemosphere ; 294: 133822, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35120960

RESUMO

An innovative cycled column test with supporting batch equilibrium and kinetic analysis for adsorption or desorption were developed for evaluation of adsorption behavior of soils. Non-equilibrium adsorption was observed in the cycled column tests as the traditional testing methods. The isotherm of local equilibrium of the soil was conducted based on the testing results within a relatively short duration with simple analysis. The concentration curves of influent and effluent of the cycled column tests were simulated by dual-porosity (DP) model with a modified inlet boundary. Based on the modeling results, the isotherm of local equilibrium is close to that of the mobile phase adsorption capacity, whereas the immobile phase of the soil is nearly inactive in the retardation of the contaminants. The testing results from cycled column tests are hardly interfered by desorption or the sorption rate according to the modeling for corresponding scenarios. The cycled column test can be used as an alternative or supplementary method to the traditional column test for the determination of local equilibrium isotherm, with advantages of shorter testing duration and easier data analysis.


Assuntos
Poluentes do Solo , Solo , Adsorção , Cinética , Poluentes do Solo/análise
3.
J Anal Test ; : 1-27, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35039787

RESUMO

Point-of-care testing (POCT), as a portable and user-friendly technology, can obtain accurate test results immediately at the sampling point. Nowadays, microfluidic paper-based analysis devices (µPads) have attracted the eye of the public and accelerated the development of POCT. A variety of detection methods are combined with µPads to realize precise, rapid and sensitive POCT. This article mainly introduced the development of electrochemistry and optical detection methods on µPads for POCT and their applications on disease analysis, environmental monitoring and food control in the past 5 years. Finally, the challenges and future development prospects of µPads for POCT were discussed.

4.
Front Cardiovasc Med ; 8: 710023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869624

RESUMO

Background: Uromodulin, also named Tamm Horsfall protein, has been associated with renal function and regulation of sodium homeostasis. We aimed to examine the associations of serum uromodulin levels and its genetic variants with longitudinal blood pressure (BP) changes and hypertension incidence/risk. Methods: A total of 514 participants from the original Baoji Salt-Sensitive Study cohort were genotyped to examine the associations of genetic variations in uromodulin gene with the longitudinal BP changes and the incidence of hypertension over 8 years of follow-up. In addition, 2,210 subjects from the cohort of Hanzhong Adolescent Hypertension Study were used to investigate the relationships between serum uromodulin levels and the risk of hypertension. Results: SNPs rs12917707 and rs12708631 in the uromodulin gene were significantly associated with the longitudinal BP changes over 8 years of follow-up. SNP rs12708631 was significantly associated with the incidence of hypertension over 8 years. In addition, gene-based analyses supported the associations of uromodulin gene with the longitudinal BP changes and hypertension incidence in Baoji Salt-Sensitive Study cohort. Furthermore, serum uromodulin levels in the hypertensive subjects were lower than in the normotensive subjects (25.5 ± 1.1 vs. 34.7 ± 0.7 ng/mL). Serum uromodulin levels decreased gradually as BP levels increased (34.6, 33.2, 27.8, and 25.0 ng/mL for subjects with normotension, high-normal, grade 1 hypertension, and grade 2 hypertension, respectively). Serum uromodulin was significantly associated with the lower risk of hypertension [0.978 (0.972-0.984)] in Hanzhong Adolescent Hypertension Study cohort. Conclusion: This study shows that uromodulin is associated with blood pressure progression and development of hypertension.

5.
Hum Mol Genet ; 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34962261

RESUMO

Thyroid dysfunction is a common endocrine disease measured by thyroid-stimulating hormone (TSH) level. Although more than 70 genetic loci associated with TSH have been reported through genome-wide association studies (GWASs), the variants can only explain a small fraction of the thyroid function heritability. To identify novel candidate genes for thyroid function, we conducted the first large-scale transcriptome-wide association study (TWAS) for thyroid function using GWAS-summary data for TSH levels in up to 119 715 individuals combined with pre-computed gene expression weights of six panels from four tissue types. The candidate genes identified by TWAS were further validated by TWAS replication and gene expression profiles. We identified 74 conditionally independent genes significantly associated with thyroid function, such as PDE8B (P = 1.67 × 10-282), PDE10A (P = 7.61 × 10-119), NR3C2 (P = 1.50 × 10-92), and CAPZB (P = 3.13 × 10-79). After TWAS replication using UKBB datasets, 26 genes were replicated for significant associations with thyroid-relevant diseases/traits. Among them, 16 gene were causal for their associations to thyroid-relevant diseases/traits and further validated in differential expression analyses, including two novel genes (MFSD6 and RBM47) that did not implicate in previous GWASs. Enrichment analyses detected several pathways associated with thyroid function, such as the cAMP signaling pathway (P = 7.27 × 10-4), hemostasis (P = 3.74 × 10-4), and platelet activation, signaling, and aggregation (P = 9.98 × 10-4). Our study identified multiple candidate genes and pathways associated with thyroid function, providing novel clues for revealing the genetic mechanisms of thyroid function and disease.

6.
J Clin Hypertens (Greenwich) ; 23(12): 2115-2123, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34846782

RESUMO

Corin, a transmembrane serine protease that can cleave pro-atrial natriuretic peptide (Pro-ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt-Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7-day low salt diet (3 g/day) and a 7-day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low-salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low-salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high-salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow-up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene-based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8-year follow-up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension.


Assuntos
Hipertensão , Serina Endopeptidases , Adulto , Pressão Sanguínea/genética , China/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Incidência , Polimorfismo de Nucleotídeo Único , Serina Endopeptidases/genética
7.
World J Clin Cases ; 9(26): 7850-7856, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34621837

RESUMO

BACKGROUND: Primary omental tumors are uncommon, and omental fibromas account for 2% of these tumors. Due to the low incidence of omental fibromas and the limited relevant literature, it is challenging for clinicians to make an accurate diagnosis of this condition, especially before surgery. CASE SUMMARY: A 30-year-old man was admitted to the hospital because of a left epididymal mass with vague discomfort for more than 1 mo. A physical examination was performed, and the findings showed that the epididymal mass may have entered the abdominal cavity. Pelvic computed tomography was performed in our hospital and revealed a left inguinal hernia with a mass in the hernial contents, and no masses were found in the left epididymis. A traditional inguinal hernia incision was made. Intraoperative hernia contents were found to be of the greater omentum, and a 2.5 cm-diameter mass was found at the distal end of the greater omentum. The scrotum and epididymis did not exhibit other masses. Then, the mass of the greater omentum was excised. Intraoperative frozen pathological examination suggested a spindle cell tumor. The postoperative pathological examination suggested that the mass was an omental angiofibroma. Postoperatively, the patient recovered well and was discharged. Outpatient re-examinations were performed at 1 mo and half a year after the operation and showed no obvious abnormalities. CONCLUSION: Due to the low morbidity rate associated with and latent nature of omental tumors, these tumors are difficult to diagnose preoperatively; thorough medical history taking, detailed physical examinations, and necessary imaging auxiliary examinations can help clinicians diagnose and treat these cases.

8.
NPJ Parkinsons Dis ; 7(1): 79, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504106

RESUMO

Genome-wide association study (GWAS) has seen great strides in revealing initial insights into the genetic architecture of Parkinson's disease (PD). Since GWAS signals often reside in non-coding regions, relatively few of the associations have implicated specific biological mechanisms. Here, we aimed to integrate the GWAS results with large-scale expression quantitative trait loci (eQTL) in 13 brain tissues to identify candidate causal genes for PD. We conducted a transcriptome-wide association study (TWAS) for PD using the summary statistics of over 480,000 individuals from the most recent PD GWAS. We identified 18 genes significantly associated with PD after Bonferroni corrections. The most significant gene, LRRC37A2, was associated with PD in all 13 brain tissues, such as in the hypothalamus (P = 6.12 × 10-22) and nucleus accumbens basal ganglia (P = 5.62 × 10-21). We also identified eight conditionally independent genes, including four new genes at known PD loci: CD38, LRRC37A2, RNF40, and ZSWIM7. Through conditional analyses, we demonstrated that several of the GWAS significant signals on PD could be driven by genetically regulated gene expression. The most significant TWAS gene LRRC37A2 accounts for 0.855 of the GWAS signal at its loci, and ZSWIM7 accounts for all the GWAS signals at its loci. We further identified several phenotypes previously associated with PD by querying the single nucleotide polymorphisms (SNPs) in the final model of the identified genes in phenome databases. In conclusion, we prioritized genes that are likely to affect PD by using a TWAS approach and identified phenotypes associated with PD.

9.
Mol Ther Oncolytics ; 22: 326-335, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34553022

RESUMO

Drug resistance is a key factor in the treatment failure of clinical non-small cell lung cancer (NSCLC) patients after adjuvant chemotherapy. Here, our results provide the first evidence that eukaryotic translation initiation factor 2b subunit delta (EIF2B4)-Stratifin (SFN) fusion and increased SFN expression are associated with chemotherapy tolerance and activation of the phosphatidylinositol 3 kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) signaling pathway in NSCLC patients, suggesting that SFN might have potential prognostic value as a tumor biomarker for the prognosis of patients with NSCLC.

12.
Hum Mol Genet ; 31(2): 300-308, 2021 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-34409462

RESUMO

Although >80 psoriasis genetic risk loci have been reported through genome-wide association studies (GWASs), the genetic mechanism of psoriasis remains unclear. To identify novel candidate genes associated with psoriasis and reveal the potential effects of genetic factors in the development of psoriasis, we conducted a transcriptome-wide association study (TWAS) based on summary statistics from GWAS of psoriasis (5175 cases and 447 089 controls) and gene expression levels from six tissues datasets (blood and skin). We identified 11 conditionally independent genes for psoriasis after Bonferroni corrections, such as the most significant genes UBLCP1 (PYFS = 2.98 × 10-16) and LCE3C (PSNSE = 9.72 × 10-12, PSSE = 6.24 × 10-12). The omnibus test identified additional five genes associated with psoriasis via the joint association model from multiple reference tissues. Among the 16 identified genes, 5 genes (CTSW, E1F1AD, KLRC3, FIBP and EFEMP2) were regarded as novel genes for psoriasis. We evaluated the 16 candidate genes by querying public databases and identified 11 differentially expressed genes and 8 genes proved by the knockout mice models. Through GO enrichment analyses, we found that TWAS genes were enriched in the known GO terms associated with skin development, such as cornified envelope (P = 4.80 × 10-8) and peptide cross-linking (P = 1.50 × 10-7). Taken together, our results detected multiple novel candidate genes for psoriasis, providing clues for understanding the genetic mechanism of psoriasis.


Assuntos
Psoríase , Transcriptoma , Animais , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Camundongos , Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética , Transcriptoma/genética
13.
J Clin Hypertens (Greenwich) ; 23(10): 1897-1906, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34363725

RESUMO

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt-Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high-salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high-salt diet than on a low-salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high-salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low-salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.


Assuntos
Hipertensão , Cloreto de Sódio na Dieta , Adulto , Pressão Sanguínea/genética , Dieta Hipossódica , Humanos , Hipertensão/genética , Cloreto de Sódio na Dieta/efeitos adversos , Uromodulina/genética
14.
World J Emerg Med ; 12(3): 179-184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34141031

RESUMO

BACKGROUND: Neuroendocrine dysfunction after traumatic brain injury (TBI) has received increased attention due to its impact on the recovery of neural function. The purpose of this study is to investigate the incidence and risk factors of adrenocortical insufficiency (AI) after TBI to reveal independent predictors and build a prediction model of AI after TBI. METHODS: Enrolled patients were grouped into the AI and non-AI groups. Fourteen preset impact factors were recorded. Patients were regrouped according to each impact factor as a categorical variable. Univariate and multiple logistic regression analyses were performed to screen the related independent risk factors of AI after TBI and develop the predictive model. RESULTS: A total of 108 patients were recruited, of whom 34 (31.5%) patients had AI. Nine factors (age, Glasgow Coma Scale [GCS] score on admission, mean arterial pressure [MAP], urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, diffuse axonal injury [DAI], and skull base fracture) were probably related to AI after TBI. Three factors (urinary volume [X 4], serum sodium level [X 5], and DAI [X 8]) were independent variables, based on which a prediction model was developed (logit P= -3.552+2.583X 4+2.235X 5+2.269X 8). CONCLUSIONS: The incidence of AI after TBI is high. Factors such as age, GCS score, MAP, urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, DAI, and skull base fracture are probably related to AI after TBI. Urinary volume, serum sodium level, and DAI are the independent predictors of AI after TBI.

15.
Huan Jing Ke Xue ; 42(6): 2691-2698, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032068

RESUMO

Ozone pollution in Handan has become severe in recent years and in the summer of 2018, the average maximum daily 8-hour average ozone concentration in Handan was 175 µg·m-3 with a maximum of 257 µg·m-3. Ozone concentrations exceeded the National Air Quality Grade Ⅱ Standard in 59% of cases. In this study, the H2O2/HNO3 indicator was applied to analyze summertime ozone sensitivity in Handan using the WRF-CMAQ modeling system. The results showed that H2O2/HNO3 was more appropriate than other ozone indicators, both theoretically and based on simulation outputs. The good simulation effect of CMAQ on H2O2 and HNO3 was attributed to fine emission inventory and grid resolution. The H2O2/HNO3 simulation results showed that the relative importance of a VOCs-limited regime decreased month by month; a VOCs-NOx-mixed-limited regime was dominant in June; and a NOx-limited regime was more dominant in July and August than in June. The remarkable spatial difference in VOCs and NOx emission ratios among the counties of Handan led to differences in ozone sensitivity. The VOCs-limited regime was concentrated in counties where VOCs/NOx emission ratios were lower than 1.7. Southern counties had a NOx-limited regime, where VOCs/NOx emission ratios were higher than 6.9. Counties with VOCs/NOx emission ratios varying from 1.7 to 6.9 were more susceptible to both VOCs and NOx. According to these results, the transition range of HCHO/NO2, O3/HNO3, and O3/NOx ratios were adjusted to 0.35-0.6, 20-35, and 10-25 respectively. Adjusting the transition range of H2O2/(O3+NO2) was not effective, indicating that this indicator may not be applicable to Handan.

16.
Environ Pollut ; 283: 117393, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34034021

RESUMO

The sorption behavior of phthalate additives in plastic and microplastic litter is an important process controlling the exposure, net health risk and ecotoxicity of these co-occurring pollutants. Plastic crystallinity and particle morphology are hypothesized to be important variables for microplastics sorption behavior, but to date there have been few direct studies to explicitly test for the influence of these parameters. To address this, in this study we explored the sorption of dibutyl phthalate (DBP) as a probe molecule to diverse polyethylene microplastics including irregularly-shaped pure polyethylene microplastics (IPPM), black plastic film microplastics (BPFM), white plastic film microplastics (WPFM), and commercial microspheres (CM), which had crystallinities ranging from 17 to 99%. Sorption kinetics for all materials could be well represented with both a pseudo-first-order (R2 = 0.87-0.93) and pseudo-second-order model (R2 = 0.87-0.93). Further, sorption was highly linear in the concentration range of 0.5-10 mg L-1, with no greater performance from a linear sorption model (R2 = 0.96-0.99) than the non-linear Freundlich or Temkin sorption models. The partition coefficient (Kd) of DBP sorption onto IPPM, BPFM, WPFM and CMs were 1974.55 L kg-1, 1483.85 L kg-1, 1477.45 L kg-1 and 509.37 L kg-1, respectively, showing a significant decrease with increasing crystallinity (r2 = 0.98). The particle size of microplastics (27-1000 µm) is, however, an indecisive factor affecting their sorption behavior for DBP in this study. This study provides new insight that crystallinity plays a governing role on the sorption of phthalate from microplastic. This should be considered in future exposure studies and assessments of phthalates from plastics and microplastics.


Assuntos
Microplásticos , Poluentes Químicos da Água , Adsorção , Dibutilftalato , Ácidos Ftálicos , Plásticos , Polietileno
17.
Sci Total Environ ; 781: 146712, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33812102

RESUMO

Potential release quantity and quality of dissolved organic matter (DOM) from hydrochar (HDOM) in various environmental conditions were investigated. Corn cobs were utilized as model agricultural residue to prepare the hydrochar. Four extracts, ultra-pure water, acid solution, alkali solution and salt solution, and two temperatures, 20 °C and 60 °C, were adopted to imitate various environmental conditions. Excitation-emission spectrophotometry with parallel factor analysis was used to evaluate the chemical properties of HDOM. The results showed that the dissolved organic carbon in the HDOM was high, ranging from 46 to 268 mg g-1. Four components were confirmed in the HDOM: mixed substances of humic-like and protein-like components, marine humic-like substances, terrestrial humic-like substances and tyrosine-like substances. Alkalinity and high temperature conditions could enhance the leaching amount of HDOM, particularly humic-like substances, and change the relative proportion of components and the chemical quality. In addition, values of the fluorescence indexes indicated that the HDOM was high microbial availability. Released HDOM may result in significant impacts in ecosystem functionality. These findings reveal the potential release characteristics of HDOM in the environment, opening new doors to understanding the environmental impacts of hydrochar and guiding its rational application.

18.
Schizophr Bull ; 47(6): 1642-1652, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33772305

RESUMO

Since the bipolar disorder (BD) signals identified by genome-wide association study (GWAS) often reside in the non-coding regions, understanding the biological relevance of these genetic loci has proven to be complicated. Transcriptome-wide association studies (TWAS) providing a powerful approach to identify novel disease risk genes and uncover possible causal genes at loci identified previously by GWAS. However, these methods did not consider the importance of epigenetic regulation in gene expression. Here, we developed a novel epigenetic element-based transcriptome-wide association study (ETWAS) that tested the effects of genetic variants on gene expression levels with the epigenetic features as prior and further mediated the association between predicted expression and BD. We conducted an ETWAS consisting of 20 352 cases and 31 358 controls and identified 44 transcriptome-wide significant hits. We found 14 conditionally independent genes, and 10 genes that did not previously implicate with BD were regarded as novel candidate genes, such as ASB16 in the cerebellar hemisphere (P = 9.29 × 10-8). We demonstrated that several genome-wide significant signals from the BD GWAS driven by genetically regulated expression, and NEK4 explained 90.1% of the GWAS signal. Additionally, ETWAS identified genes could explain heritability beyond that explained by GWAS-associated SNPs (P = 5.60 × 10-66). By querying the SNPs in the final models of identified genes in phenome databases, we identified several phenotypes previously associated with BD, such as schizophrenia and depression. In conclusion, ETWAS is a powerful method, and we identified several novel candidate genes associated with BD.


Assuntos
Transtorno Bipolar/genética , Epigênese Genética/genética , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla , Transcriptoma/genética , Adulto , Humanos
19.
J Hypertens ; 39(9): 1817-1825, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33783375

RESUMO

OBJECTIVE: Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans. METHODS: Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years. RESULTS: The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up. CONCLUSIONS: This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.


Assuntos
Hipertensão , Cloreto de Sódio na Dieta , Adulto , Animais , Pressão Sanguínea/genética , Proteínas Sanguíneas , China/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Incidência , Piperazinas , Polimorfismo de Nucleotídeo Único , Gravidez , Ratos
20.
Genome Med ; 13(1): 48, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771188

RESUMO

BACKGROUND: Childhood obesity is reported to be associated with the risk of many diseases in adulthood. However, observational studies cannot fully account for confounding factors. We aimed to systematically assess the causal associations between childhood body mass index (BMI) and various adult traits/diseases using two-sample Mendelian randomization (MR). METHODS: After data filtering, 263 adult traits genetically correlated with childhood BMI (P < 0.05) were subjected to MR analyses. Inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods were used to estimate the causal effects. Multivariable MR analysis was performed to test whether the effects of childhood BMI on adult traits are independent from adult BMI. RESULTS: We identified potential causal effects of childhood obesity on 60 adult traits (27 disease-related traits, 27 lifestyle factors, and 6 other traits). Higher childhood BMI was associated with a reduced overall health rating (ß = - 0.10, 95% CI - 0.13 to - 0.07, P = 6.26 × 10-11). Specifically, higher childhood BMI was associated with increased odds of coronary artery disease (OR = 1.09, 95% CI 1.06 to 1.11, P = 4.28 × 10-11), essential hypertension (OR = 1.12, 95% CI 1.08 to 1.16, P = 1.27 × 10-11), type 2 diabetes (OR = 1.36, 95% CI 1.30 to 1.43, P = 1.57 × 10-34), and arthrosis (OR = 1.09, 95% CI 1.06 to 1.12, P = 8.80 × 10-9). However, after accounting for adult BMI, the detrimental effects of childhood BMI on disease-related traits were no longer present (P > 0.05). For dietary habits, different from conventional understanding, we found that higher childhood BMI was associated with low calorie density food intake. However, this association might be specific to the UK Biobank population. CONCLUSIONS: In summary, we provided a phenome-wide view of the effects of childhood BMI on adult traits. Multivariable MR analysis suggested that the associations between childhood BMI and increased risks of diseases in adulthood are likely attributed to individuals remaining obese in later life. Therefore, ensuring that childhood obesity does not persist into later life might be useful for reducing the detrimental effects of childhood obesity on adult diseases.


Assuntos
Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Fenômica , Característica Quantitativa Herdável , Adulto , Idoso , Criança , Pré-Escolar , Dieta , Pleiotropia Genética , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Análise Multivariada , Obesidade Pediátrica/genética
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