Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacogenomics of HIV Therapy - Atazanavir Bilirubin-related Side Effects

ABSTRACT:

This is an evaluation of genetic associations with atazanavir (ATV) discontinuation for bilirubin-related causes within 12 months of treatment. Patients were treated at an HIV primary care clinic in Nashville TN from 1998 to 2012. A previously known SNP in UGT1A1 (rs887829) was used to define metabolizer genotypes (extensive, intermediate, slow metabolizer). Over 500,000 SNPs from genome-wide genotyping were used to define MDS (Multidimensional Scaling) coordinates to account for population stratification. Patients were defined as cases if they discontinued ATV for bilirubin-related causes within 12 months of treatment, otherwise they were defined as controls if they did not stop treatment.

Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of black, 21.4% of Hispanic, and 8.6% of white patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 (95% C.I.: 1.7 to 31.5; p = 0.007). Among 152 white patients the HR was 14.4 (95% CI: 2.6 to 78.7; p = 0.002), but among 153 black patients the HR was 0.8 (95% C.I. 0.05 to 12.7; p = 0.87).

PROVIDER: phs001484 | dbGaP |

SECONDARY ACCESSION(S): PRJNA417885PRJNA417884

REPOSITORIES: dbGaP

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	GapExchange_phs001484.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001484.Atazanavir_Bilirubin.v1.p1.MULTI.pdf	Pdf
	manifest_phs001484.Atazanavir_Bilirubin.v1.p1.c1.DS-HIV-IRB.pdf	Pdf
	datadict_v2.xsl	Other

Items per page:

1 - 5 of 15

Similar Datasets

Pharmacogenetics of Efavirenz Discontinuation for Reported CNS Symptoms

Project description:This is an evaluation of genetic associations with efavirenz (EFV) discontinuation for central nervous system (CNS) symptoms within 12 months of treatment. Patients were treated at an HIV primary care clinic in Nashville TN from 1998 to 2012. Previously known SNPs in <a href="https://www.ncbi.nlm.nih.gov/gene/1555">CYP2B6</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/1548">CYP2A6</a> were used to define metabolizer genotypes (extensive, intermediate, slow metabolizer). Over 500,000 SNPs from genome-wide genotyping were used to define MDS (Multidimensional Scaling) coordinates to account for population stratification. Patients were defined as cases if they discontinued EFV for CNS symptoms within 12 months, otherwise they were defined as controls if they did not stop treatment. Among 563 evaluable participants, the hazard ratio for EFV discontinuation for CNS symptoms was 4.9 (95% C.I. 1.9 TO 12.4, p=0.001) in slow metabolizers compared to extensive metabolizers. This association was very significant in Whites 6.5 (95% CI: 2.3 to 18.8; p = 0.001), but not in Blacks 2.6 (95% C.I. 0.5 to 14.1; p = 0.27). The reason for this difference by race is not clear and warrants further investigation.

| phs001253 | dbGaP

Genomic profiles and survival prognosticators in African-American patients with acute myeloid leukemia

Project description:Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 Black patients with AML (Alliance) and compared somatic mutation frequencies with those of 323 White patients (BeatAML). Seventy-three percent of 162 recurrent gene mutations identified in Black patients, including a novel PHIP alteration detected in 7% of patients, were found in only ≤1 White patient. Black patients with myelodysplasia-related AML were younger than White patients suggesting intrinsic and/or extrinsic dysplasia-causing stressors. On multivariable outcome analyses of Black patients, NPM1 and NRAS mutations associated with inferior disease-free and IDH1/2 mutations with reduced overall survival. Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and White NPM1-mutated patients. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic-risk stratification changed risk-group assignment for one-third of Black patients and improved their outcome prediction.

2024-05-31 | GSE266498 | GEO

Genomic profiles and survival prognosticators in African-American patients with acute myeloid leukemia

2024-05-01 | GSE266099 | GEO

Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response

Project description:It is estimated that 10% of COVID survivor still experience from complaints months after infection. Here we collected blood from 95 patients in the P4O2 COVID-19 study and performed RNA-seq at 3-6 months and 12-15 after infection. Our aim was to discover biomarkers related to long COVID and perform unsupervised clustering to potentially reveal pathological underlying mechanism for long COVID

2024-05-22 | GSE267625 | GEO

Molecular Dysregulation Underlying Racial Disparity in Hepatocellular Carcinoma (HCC)

Project description:Hepatocellular carcinoma (HCC) is a highly fatal disease with mortality running parallel to its incidence. For HCC patients, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic (white) patients. There is a gap of knowledge in our understanding of the molecular mechanism underlying the HCC racial disparity between AA/Black and white patients. To address this issue, we analyzed existing RNA-sequencing (RNA-seq) data from HCC patients in the TCGA database, and performed RNA-seq in 14 white and 19 AA/Black HCC patients from Virginia Commonwealth University. In both analysis the only pathway which showed statistically significant activation in AA/Black patients, compared to white patients, was type I interferon (IFN-I) signaling. A four gene signature of IFN-I-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors compared to their white counterparts. HCC is a disease of chronic inflammation and IFN-I function as a pro-inflammatory and immunosuppressive cytokine. These findings suggest a potential role of IFN-I in conferring disparity in AA/Black HCC patients.

2023-09-15 | GSE223795 | GEO

Transcriptomic analysis of pancreatic adenocarcinoma specimens obtained from Black and White patients

Project description:In pancreatic cancer clinical trials, Black patients are under-represented while having higher morbidity and mortality rates as compared to other racial groups. Multiple factors, including socioeconomic and lifestyle factors may contribute to this disparity, but genomic contributions remain unclear. In an exploratory project to identify genes that may contribute to differences in survival between Black and White patients with pancreatic cancer, transcriptomic sequencing of over 24,900 genes was performed in human pancreatic tumor and non-tumor tissue obtained from Black and White patients. Over 4,400 genes were differentially expressed in tumor and non-tumor tissue, irrespective of race. Of these 4,400 genes, four (AGR2, POSTN, TFF1, and CP) met the pre-defined statistical threshold for upregulation in pancreatic tumor tissue; these findings were confirmed by quantitative PCR. Transcriptomic analysis of pancreatic tumor tissue in Black and White patients revealed differential expression in 1,200 genes. Non-tumor and tumor gene expression differences within each race were assessed, revealing over 1,500 tumor-specific differentially expressed genes in pancreatic tumor and non-tumor tissue from Black patients. We identified TSPAN8 as a potential tumor-specific gene significantly overexpressed in pancreatic tumor tissue in Black patients as compared to White patients. Using Ingenuity Pathway Analysis software to compare the race-associated gene expression profiles, over 40 canonical pathways were identified to be potentially impacted by the gene expression differences between the races. Heightened expression of TSPAN8 was associated with poor overall survival, suggesting TSPAN8 as one potential genetic factor contributing to the differential outcomes in Black patients with pancreatic cancer, supporting the potential utility of larger genomic studies to further explore the role of TSPAN8 in pancreatic cancer.

2023-01-19 | GSE211398 | GEO

MiRNome profiling of glioblastoma tissues and peritumoral regions

Project description:Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. Its prognosis is inexorably unfavorable, as these tumors drive affected patients to death usually within 15 months after diagnosis (short term survivors, ST), with the only exception of a small fraction of patients (long term survivors, LT) surviving longer than 36 months. Even after the frontline therapeutic approach, including surgical resection followed by chemo- and radiotherapy, the cause of death in most cases is tumor recurrence, which occurs in peritumoral tissues in about 95% of patients. Here, we provide a comprehensive molecular analysis of a set of ST and LT samples derived from frankly tumoral areas (C) and from the peritumoral regions (P) of the same patients. By performing microRNA deep sequencing, we collected data showing that P areas differ from healthy white matter, but share with C samples, a number of microRNAs

2017-03-08 | E-MTAB-3239 | biostudies-arrayexpress

NanoString PanCancer Immune Panel in Black and White Breast Cancer Patients in the Women's Circle of Health Study (WCHS)

Project description:NanoString PanCancer Immune Panel with customized codesets from a total of 367 Black and White breast cancer patients in WCHS

2020-12-18 | GSE163418 | GEO

Affymetrix SNP array data for Dwarf and Rhode Island Red chicken samples

Project description:The genetic foundation of chicken tail feather color is not very well studied to date, though that of body feather color is extensively explored. In the present study, we used a synthetic chicken dwarf line (DW), which was originated from the hybrids between a black tail chicken breed, Rhode Island Red (RIR) and a white tail breed, Dwarf Layer (DL), to understand the genetic rules of the white/black tail color. The DW line still contain the individuals with black or white tails, even if the body feather are predominantly red, after more than ten generation of self-crossing and being selected for the body feather color. We firstly performed four crosses using the DW line chickens including black tail male to female, reciprocal crosses between the black and white, and white male to female to elucidate the inheritance pattern of the white/black tail. We found that (i) the white/black tail feather colors are independent of body feather color and (ii) the phenotype are autosomal simple trait and (iii) the white are dominant to the black in the DW lines. Furtherly, we performed a genome-wide association (GWA) analysis to determine the candidate genomic regions underlying the tail feather color by using black tail chickens from the RIR and DW chickens and white individuals from DW lines.

2019-05-02 | GSE130568 | GEO

Differential Gene Expression between African American and European American Colorectal Cancer Patients

Project description:The incidence and mortality of colorectal cancer (CRC) is higher in African Americans (AAs) than in other ethnic groups in the U. S., but reasons for the disparities are unknown. We performed gene expression profiling and microsatellite instability (MSI) analysis of sporadic CRCs from AAs vs. European Americans (EAs) to assess the contribution to CRC disparities. We evaluated gene expression of 43 AA and 43 EA CRC tumors matched by stage and 40 normal colon tissues using the Agilent human whole genome 4x44K cDNA arrays. Gene and pathway analysis were performed using Significance Analysis of Microarrays (SAM), 10-fold Cross Validation (10-fCV) and Ingenuity Pathway Analysis (IPA). MSI analysis was assessed with five NIH Bethesda markers. SAM revealed that 95 genes were differentially expressed between AA and EA patients at a false discovery rate of <5%. A 10f-CV demonstrated that 9 genes were differentially expressed between AA and EA with an accuracy of 97%. Nine genes (CRYBB2, PSPH, ADAL, VSIG10L, C17orf81, ARSE, ANKRD36B, ZNF835, ARHGAP6) were validated and differential expression confirmed by qRT-PCR in independent test set of 21 patients (10 AA, 11 EA). We also analyzed MSI in 57 of the CRC subjects. Overall, 15.8% of CRC patients had MSI, with a higher rate observed in EA (20%) than in AA (12%). MSI distribution by tumor site was 77% right and 23% left colon. Previously, genetic, epigenetic and environmental factors have been implicated in the etiology of CRC. Our results are the first to implicate differential gene expression in CRC disparities and support the existence of distinct tumor microenvironments in these two patients' populations. 126 total samples: 1) 43 white cancer samples; 2) 43 black cancer samples; 3) 27 white control samples; 4) 13 black control samples.

2012-05-22 | E-GEOD-28000 | biostudies-arrayexpress