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Genomic variants link to hepatitis C racial disparities.

ABSTRACT: Chronic liver diseases are one of the major public health issues in United States, and there are substantial racial disparities in liver cancer-related mortality. We previously identified racially distinct alterations in the expression of transcripts and proteins of hepatitis C (HCV)-induced hepatocellular carcinoma (HCC) between Caucasian (CA) and African American (AA) subgroups. Here, we performed a comparative genome-wide analysis of normal vs. HCV+ (cirrhotic state), and normal adjacent tissues (HCCN) vs. HCV+HCC (tumor state) of CA at the gene and alternative splicing levels using Affymetrix Human Transcriptome Array (HTA2.0). Many genes and splice variants were abnormally expressed in HCV+ more than in HCV+HCC state compared with normal tissues. Known biological pathways related to cell cycle regulations were altered in HCV+HCC, whereas acute phase reactants were deregulated in HCV+ state. We confirmed by quantitative RT-PCR that SAA1, PCNA-AS1, DAB2, and IFI30 are differentially deregulated, especially in AA compared with CA samples. Likewise, IHC staining analysis revealed altered expression patterns of SAA1 and HNF4? isoforms in HCV+ liver samples of AA compared with CA. These results demonstrate that several splice variants are primarily deregulated in normal vs. HCV+ stage, which is certainly in line with the recent observations showing that the pre-mRNA splicing machinery may be profoundly remodeled during disease progression, and may, therefore, play a major role in HCV racial disparity. The confirmation that certain genes are deregulated in AA compared to CA tissues also suggests that there is a biological basis for the observed racial disparities.

SUBMITTER: Yeh MM

PROVIDER: S-EPMC5601746 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Genomic variants link to hepatitis C racial disparities.

Yeh Matthew M MM Boukhar Sarag S Roberts Benjamin B Dasgupta Nairanjana N Daoud Sayed S SS

Oncotarget 20170801 35

Chronic liver diseases are one of the major public health issues in United States, and there are substantial racial disparities in liver cancer-related mortality. We previously identified racially distinct alterations in the expression of transcripts and proteins of hepatitis C (HCV)-induced hepatocellular carcinoma (HCC) between Caucasian (CA) and African American (AA) subgroups. Here, we performed a comparative genome-wide analysis of normal <i>vs</i>. HCV+ (cirrhotic state), and normal adjace ...[more]

PMID: 28938650

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Project description:ObjectiveTo evaluate racial and ethnic differences in women's postpartum pain scores, inpatient opioid administration, and discharge opioid prescriptions.MethodsWe conducted a retrospective cohort study of all deliveries at a single high-volume tertiary care center from December 1, 2015, through November 30, 2016. Women were included if they self-identified as non-Hispanic white, non-Hispanic black, or Hispanic; were at least 18 years of age; and did not have documented allergies to nonsteroidal antiinflammatory drugs or morphine. Medical records were queried for three outcomes: 1) patient-reported postpartum pain score (on a scale of 0-10) at discharge (dichotomized less than 5 or 5 or higher), 2) inpatient opioid dosing during postpartum hospitalization (reported as morphine milligram equivalents [MMEs] per postpartum day), and 3) receipt of an opioid prescription at discharge. The associations between each of these outcomes and maternal race-ethnicity were assessed using multivariable logistic regression models with random effects to account for clustering by discharge physician. A sensitivity analysis was conducted in which women of different race and ethnicity were matched using propensity scores.ResultsA total of 9,900 postpartum women were eligible for analysis. Compared with non-Hispanic white women, Hispanic and non-Hispanic black women had significantly greater odds of reporting a pain score of 5 or higher (adjusted odds ratio [aOR] 1.61, 95% 1.26-2.06 and aOR 2.18, 95% 1.63-2.91, respectively) but received significantly fewer inpatient MMEs/d (adjusted β -5.03, 95% CI -6.91 to -3.15, and adjusted β -3.54, 95% CI -5.88 to -1.20, respectively). Additionally, Hispanic and non-Hispanic black women were significantly less likely to receive an opioid prescription at discharge (aOR 0.80, 95% CI 0.67 to -0.96 and aOR 0.78, 95% CI 0.62-0.98) compared with non-Hispanic white women. Results of the propensity score analysis largely corroborated those of the primary analysis, with the exception that the difference in inpatient MMEs/d between non-Hispanic white and non-Hispanic black women did not reach statistical significance.ConclusionHispanic and non-Hispanic black women experience disparities in pain management in the postpartum setting that cannot be explained by less perceived pain.

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Genomic variants link to hepatitis C racial disparities.

Publications

Genomic variants link to hepatitis C racial disparities.

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