Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects: A Strobe Compliant Article.
Ontology highlight
ABSTRACT:
SUBMITTER: Oussalah A
PROVIDER: S-EPMC4616369 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Publications
Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects: A Strobe Compliant Article.
Oussalah Abderrahim A Bosco Paolo P Anello Guido G Spada Rosario R Guéant-Rodriguez Rosa-Maria RM Chery Céline C Rouyer Pierre P Josse Thomas T Romano Antonino A Elia Maurizzio M Bronowicki Jean-Pierre JP Guéant Jean-Louis JL
Medicine 20150601 22
Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy. Coding variants were replicated in 227 elderly subjects from the same area. We identified 4 mi ...[more]
Similar Datasets
Project description:The aim of the study was to review the distribution, current trends, and microbiological characteristics of bacterial pathogens isolated from dacryocystitis patients in China during the last 15 years.This is a retrospective multiple-center noncomparative case series. The medical records of 15,452 consecutive patients from 7 cities diagnosed as having dacryocystitis between 2002 and 2016 were reviewed. The patients' demographics, microbiological data, and antibiotic sensitivity were reviewed and analyzed.A total of 3344 lacrimal sac content cultures were taken (21.6%) during the study period. A pathogen was identified in 1996 samples (59.7%), with bacterial isolates accounting for 1902 of the positive cultures (95.3%). Gram-positive isolates, gram-negative isolates, and anaerobic bacteria were found in 1218 (61.0%), 607 (30.4%), and 285 (14.3%) samples, respectively. An increase in gram-positive isolates over the study duration was found (P?=?.003). The predominant isolates were coagulase negative Staphylococci (485, 25.5%), Staphylococcus aureus (186, 9.8%), Pseudomonas aeruginosa (184, 9.7%), and Haemophilus influenzae (152, 9.0%). There was a trend toward increasing resistance to erythromycin from 10.5% during the first 5 years of the study to 20.7% during the last 5 years (P?<?.001). Antimicrobial susceptibility testing showed that gatifloxacin was the most effective drug against most of gram-positive, gram-negative, and anaerobic bacteria.The microbial culture rate of dacryocystitis in China is low. There was an increase in the percentage of gram-positive bacteria over time. The sensitivity of gram-positive isolates to tested antibiotics is relatively low compared with that of gram-negative isolates. Our data show that the empiric use of fourth-generation fluoroquinolones in refractory dacryocystitis may be justified.
| S-EPMC6039673 | biostudies-literature
Project description:To evaluate the visual outcomes of cataract surgery in patients with uveitis, and to determine risk factors for the recurrence of uveitis and postoperative complications.Eighty patients with uveitis who underwent phacoemulsification with intraocular lens (IOL) implantation were included in this retrospective study. We analyzed the following data: patient characteristics, medications used, visual acuity, and complications of cataract surgery.The mean?±?standard deviation time from cataract surgery to the last visit was 20.8?±?10.4 months. Best-corrected visual acuity improved significantly after surgery (P?<?.001). The visual outcome was worse in patients with Behçet disease than in patients with other etiologies of uveitis. Gender (P?=?.018) and IOL type (P?=?.020) were significantly associated with recurrent uveitis after surgery. The incidence of recurrent inflammation was not significantly different between patients who did or did not receive systemic therapy (P?=?.43). Perioperative systemic therapies (P?=?.011) and recurrent uveitis within 3 months of surgery (P?=?.043) were associated with posterior capsular opacification. Perioperative systemic therapies (P?=?.026) and recurrent uveitis after surgery (P?=?.006) were also significantly associated with cystoid macular edema.Patients with uveitis could benefit from cataract surgery. Patients with Behçet disease had worse postoperative prognosis than patients with other etiologies of uveitis. A heparin-surface-modified IOL may reduce the incidence of recurrent inflammation.
| S-EPMC5627807 | biostudies-literature
Project description:Recently, researchers have focused on the embodied sense of self (ESS), which consists of the minimal and narrative selves. Although a study demonstrated that the ESS is related to brain dysfunction empirically, the subjective aspects of the ESS, and a systematic approach to it, have not yet been examined in brain-damaged patients. To examine this, we measured the ESS of patients with brain tumors before and after awake craniotomy.A self-reported questionnaire called the Embodied Sense of Self Scale (ESSS) was used to measure the ESS in patients with brain tumors before and after surgery. For comparison, age-matched controls also completed the ESSS.The ESSS scores of the patients with brain tumors before surgery were higher than those of the controls and improved after surgery. Before surgery, patients with left hemispheric lesions had a poorer ESSS than those with right hemispheric lesions. Episodic memory disturbance was highly correlated with malfunction of narrative self and ownership.Brain lesions were associated with anomalous ESSS, associated with hemispheric laterality and cognitive dysfunction.
| S-EPMC6133420 | biostudies-literature
Project description:Total serum bilirubin is associated with several clinical outcomes, including cardiovascular disease, diabetes and drug metabolism. We conducted a genome-wide association study in 619 healthy unrelated African Americans in an attempt to replicate reported findings in Europeans and Asians and to identify novel loci influencing total serum bilirubin levels. We analyzed a dense panel of over two million genotyped and imputed SNPs in additive genetic models adjusting for age, sex, and the first two significant principal components from the sample covariance matrix of genotypes. Thirty-nine SNPs spanning a 78 kb region within the UGT1A1 displayed P-values <5 × 10(-8). The lowest P-value was 1.7 × 10(-22) for SNP rs887829. None of SNPs in the UGT1A1 remained statistically significant in conditional association analyses that adjusted for rs887829. In addition, SNP rs10929302 located in phenobarbital response enhancer module was significantly associated with bilirubin level with a P-value of 1.37 × 10(-11); this enhancer module is believed to have a critical role in phenobarbital treatment of hyperbilirubinemia. Interestingly, the lead SNP, rs887829, is in strong linkage disequilibrium (LD) (r(2)≥0.74) with rs10929302. Taking advantage of the lower LD and shorter haplotypes in African-ancestry populations, we identified rs887829 as a more refined proxy for the causative variant influencing bilirubin levels. Also, we replicated the reported association between variants in SEMA3C and bilirubin levels. In summary, UGT1A1 is a major locus influencing bilirubin levels and the results of this study promise to contribute to understanding of the etiology and treatment of hyperbilirubinaemia in African-ancestry populations.
| S-EPMC3306855 | biostudies-literature
Project description:The aim of the study was to assess the independent contribution of hyperuricemia to coronary artery disease (CAD) confirmed by coronary angiography (CAG), and to explore associations between serum uric acid (SUA) level and CAD.We performed a retrospective cohort study of 5069 patients who underwent CAG. Patients were divided into groups: hyperuricemia (n?=?1178) versus nonhyperuricemia (n?=?3891) and CAD (n?=?3433) versus non-CAD (n?=?1636).The incidence of CAD was higher in the hyperuricemia group than in the nonhyperuricemia group (71.5% vs 66.6%, P?=?.002). Hyperuricemia and CAD were significantly correlated in women (odds ratio?=?1.509, 95% confidence interval, 1.106-2.057, P?=?.009). And there were trends, higher SUA quartiles were associated with higher percentage of CAD (62.3%, 68.0%, 68.9%, and 71.7% for quartiles 1, 2, 3, and 4, respectively, P?<?.001), and the incidence of 3-vessel disease increased (25.2%, 26.4%, 27.2%, and 31.1% for quartiles 1, 2, 3, and 4, respectively, P?=?.001) and that of normal vessel decreased (37.7%, 32.0%, 31.1%, and 28.3% for quartiles 1, 2, 3, and 4, respectively, P?<?.001) across quartiles, these trends were found in female group, but not in male group. The SUA level significantly increased as the number of diseased vessels increased (P?<?.001).There was an independent correlation between hyperuricemia and CAD in women. A higher SUA level was associated with a higher incidence of 3-vessel disease in women.
| S-EPMC6221642 | biostudies-other
Project description:To explore whether weight-age (W-A) could be applied in clinical practice, this study was designed to verify the normalization ability of W-A by the data from another medical center, and to access the influence of the normalization on glomerular filtration rate (GFR) values in renal patients.Both plasma clearance (pGFR) and camera-based (gGFR), which were separately scaled to W-A and body surface area (BSA), were measured for patients with diffuse renal diseases. The patients (n?=?298) were stratified according to the Chinese body mass index (BMI) criteria and were staged according to the Kidney Disease Outcome Quality Initiatives guideline based on gGFR and pGFR separately.The indices of intraclass correlation coefficient (ICC), concordance correlation coefficient (CCC), and ratio of residual standard deviation to pooled standard deviation (RSD/PSD) suggested that, for all patients and each BMI stratum, W-A was obviously better than BSA in scaling GFR. Both under pGFR or gGFR renal stages, only small amount of the patients encountered stage migrations from BSA to W-A scaled stages. The differences between any 2 of the unscaled, BSA scaled, and W-A scaled gGFR (or pGFR) were not obviously changed. Additionally, in some strata, W-A normalization is better than BSA normalization in decreasing the median bias between pGFR and gGFR.W-A is better than BSA in scaling GFR without obvious modifying GFR values and can be applied in routine clinical practice.
| S-EPMC4998260 | biostudies-literature
Project description:At present, there are no effective methods for the treatment of hemophilia B, and it has high mortality and disability. Therefore, it is very important for the carriers to carry out genetic counseling and make prenatal diagnosis. In this study, we made gene and prenatal diagnoses in a family with a novel F9 gene mutation, and report a novel F9 gene mutation.All exon sequences and flanking sequences of F9 gene were analyzed by Sanger sequencing in the proband; and then according to the F9 gene mutation in the proband, the F9 gene sequencing was performed on the family members. Based on the above results, the pathogenic mutation in F9 gene was finally identified, which was used for prenatal diagnosis.Sanger sequencing revealed c.1232G>C [p.Ser411Thr] mutation in F9 gene in the proband. c.1232G>C heterozygous mutation was also found in the proband's mother and grandmother, but male family members without hemophilia B had no this mutation. The analyses of amniotic fluid samples indicated positive sex-determining region on Y chromosome (SRY), and no c.1232G>C [p.Ser411Thr] mutation in F9 gene.We identified a pathogenic mutation in F9 gene in the family, made a prenatal diagnosis for the female carrier and reported a novel F9 gene mutation.
| S-EPMC6571360 | biostudies-literature
Project description:Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality. This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival.Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry. Cases with lung adenocarcinoma were followed until the end of 2010. Survival curves were estimated by the Kaplan-Meier method. Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma.A total of 14,518 cases were identified with lung adenocarcinoma. Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10-2.58), 1.48 (95% CI, 1.14-1.93), and 1.27 (95% CI, 1.08-1.49) for individuals with stage I + II, III, and IV diseases, respectively. The HRs for asthma were 1.41 (95% CI, 1.00-1.99) in women with stage I + II and 1.14 (95% CI, 1.04-1.26) in men with stage IV disease. For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12-1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12-1.63) for COPD + TB, 1.28 (95% CI, 1.01-1.63) for TB, and 1.15 (95%CI, 1.04-1.27) for asthma + COPD, respectively. For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72-17.71) for asthma + COPD + TB.Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma. TB is at elevated risk of mortality among men with different stages of adenocarcinoma. Asthmatic women with early-stage adenocarcinoma had increased risk of mortality.
| S-EPMC4998887 | biostudies-other
Project description:The potential association between the prognosis of the pancreatic adenocarcinoma (PAAD) and its microenvironment is unclear. This study aims to construct a prognostic index (PI) model of the PAAD microenvironment to predict PAAD patient survival outcomes.The mRNA sequencing and the clinical parameters data were obtained from The Cancer Genome Atlas. Immune and stromal scores were computed using the expression data algorithm to capture infiltration of immune and stromal cells in the PAAD tissue, where patients were categorized as high and low score groups according to these scores. Differentially expressed genes were identified using the R package LIMMA. Univariate and multivariate Cox regression analysis were conducted to select candidate survival-correlated gene signatures from the tumor microenvironment for constructing a model. The Kaplan-Meier method was used to access overall survival of the primary and validation cohorts. The immunological features of the PI model was explored using the Tumor Immune Estimation Resource (TIMER) database. Bioinformatic analyses were conducted based on the DAVID database.A total of 1266 overlapping differentially expressed genes and 49 prognosis-associated genes were identified. A 7-mRNA signature (GBP5, BICC1, SLC7A14, CYSLTR1, P2RY6, VENTX, and RAB39B) was screened for the construction of a PI model (area under the curve = 0.791). In both the primary and validation cohorts, Kaplan Meier analysis revealed that the overall survival of the high-risk group was significantly worse compared to the low-risk group (P?<?.0001, P?=?.0028 respectively). The TIMER database described that the 7 signature genes were correlated with immune infiltrating cells and tumor purity. Bioinformatic analyses revealed that these prognosis-associated genes were significantly enriched during inflammation, the defense response, would response, calcium ion transport, and plasma membrane part.A list of the prognosis-correlated genes was generated based on the PAAD microenvironment. A 7-mRNA PI model may be used for predicting the prognosis of PAAD patients.
| S-EPMC7373597 | biostudies-literature
Project description:Transforming growth factor-beta (TGF-β2) is an important cytokine regulating immune cell function. However, whether TGF-β2 controls the invasion of colorectal cancer (CRC) by immune cells is unknown. Therefore, we evaluated the expression of TGF-β2 using multiple databases and determined the relationship between TGF-β2 expression and tumor immune infiltration defined by a set of genetic markers. The analysis demonstrated that the expression of TGF-β2 is closely related to the outcome of many cancers, and this correlation was particularly strong in CRC. In addition, the increased expression of TGF-β2 was significantly associated with the expression of various markers of specific immune cell subpopulations, and overexpression of TGF-β2 was closely related to the prognosis of colon cancer patients. Moreover, TGF-β2 was related to the prognosis and infiltration of the tumor by immune cells in CRC patients. The obtained results indicate that TGF-β2 is a critical factor regulating the recruitment of immune cells and controls their infiltration into colorectal tumors. Thus, high expression of TGF-β2 not only facilitates the prognosis in CRC patients, but also may provide a new target for the treatment of CRC.
| S-EPMC7668458 | biostudies-literature