Global gene-expression analysis has shown remarkable difference between males and females in response to exposure to many diseases. Nevertheless, gene expression studies in asthmatics have so far focused on sex-combined analysis, ignoring inherent variabilities between the sexes, which potentially drive disparities in asthma prevalence. The objectives of this study were to identify (1) sex-specific differentially expressed genes (DEGs), (2) genes that show sex-interaction effects and (3) sex-specific pathways and networks enriched in asthma risk. We analyzed 711 males and 689 females and more than 2.8 million transcripts covering 20 000 genes leveraged from five different tissues and cell types (i.e. epithelial, blood, induced sputum, T cells and lymphoblastoids). Using tissue-specific meta-analysis, we identified 439 male- and 297 female-specific DEGs in all cell types, with 32 genes in common. By linking DEGs to the genome-wide association study (GWAS) catalog and the lung and blood eQTL annotation data from GTEx, we identified four male-specific genes (FBXL7, ITPR3 and RAD51B from epithelial tissue and ALOX15 from blood) and one female-specific gene (HLA-DQA1 from epithelial tissue) that are disregulated during asthma. The hypoxia-inducible factor 1 signaling pathway was enriched only in males, and IL-17 and chemokine signaling pathways were enriched in females. The cytokine-cytokine signaling pathway was enriched in both sexes. The presence of sex-specific genes and pathways demonstrates that sex-combined analysis does not identify genes preferentially expressed in each sex in response to diseases. Linking DEG and molecular eQTLs to GWAS catalog represents an important avenue for identifying biologically and clinically relevant genes.

Background

African Americans (AAs) suffer the widest gaps in chronic kidney disease (CKD) outcomes compared to Caucasian Americans (CAs) and this is because of the disparities that exist in both health and healthcare. In fact, the prevalence of CKD is 3.5 times higher in AAs compared to CAs. The disparities exist at all stages of CKD. Importantly, AAs are 10 times more likely to develop hypertension-related kidney failure and 3 times more likely to progress to kidney failure compared to CAs.

Summary

Several factors contribute to these disparities including genetic and social determinants, late referrals, poor care coordination, medication adherence, and low recruitment in clinical trials. Key Messages: The development and implementation of CKD-related evidence-based approaches, such as clinical and social determinant assessment tools for medical interventions, more widespread outreach programs, strategies to improve medication adherence, safe and effective pharmacological treatments to control or eliminate CKD, as well as the use of health information technology, and patient-engagement programs for improved CKD outcomes may help to positively impact these disparities among AAs.

Background

Chronic kidney disease is a progressive disease, which terminates in end-stage renal diseases (ESRD) that requires either dialysis or kidney transplantation for the patient to survive. There is an alarming trend in the disparities of ESRD in African Americans (AAs). Currently, AAs represent more than 30% of incident ESRD cases, yet they constitute 15% of the overall US population. Despite the reductions in mortality, increases in access to patient-centered home dialysis and preemptive kidney transplantation for the overall US ESRD population over the last decade, disparities in the care of AAs with ESRD remain largely unaffected.

Summary

This review discusses patient-, community-, and practitioner-related factors that contribute to disparities in ESRD care for AAs. In particular, the review addresses issues related to end-of-life support, the importance of Apolipoprotein-1 gene variants, and the advent of pharmacogenomics toward achieving precision care. The need for accessible clinical intelligence for the ESRD population is discussed. Several interventions and a call to action to address the disparities are presented. Key Messages: Significant disparities in ESRD care exist for AAs. Strategies to enhance patient engagement, education, accountable partnerships, and clinical intelligence may reduce these disparities.

Background

Asthma is a common childhood disease that leads to many missed days of school and parents' work. There are multiple environmental contributors to asthma symptoms and understanding the potential factors inside children's homes is crucial.

Methods

This is a dual cohort study measuring household particulate matter (PM2.5), behaviors, and factors that influence air quality and asthma symptoms in the urban homes of children (ages 6-10) with asthma; one cohort had cigarette smoke exposure in the home (n = 13) and the other did not (n = 22). Exposure data included measurements every 5 minutes for a month.

Results

In the entire study population, a large contributor to elevations in indoor PM2.5 above 35 μg/m3 was not using the stove hood when cooking (8.5% higher, CI 3.1-13.9%, p<0.005). Median PM values during cooking times were 0.88 μg/m3 higher than those during non-cooking times (95% CI 0.33-1.42). Mean monthly household PM2.5 level was significantly related to the presence of a cigarette smoker in the home (10.1 μg/m3 higher, 95% CI 5.2-15.1, p<0.001) when controlling for use of the stove hood and proximity to major roadway. There was a trend toward increased odds of persistent asthma with increases in average monthly PM2.5 (OR 1.1, 95% CI 0.97-1.3, p = 0.16).

Conclusions

Consideration of only outdoor PM2.5 may obscure potentially modifiable risks for asthma symptoms. Specifically, this preliminary study suggests that cooking behaviors may contribute to the burden of PM2.5 in the homes of children with asthma and thus to asthma symptoms.

Background

The persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system.

Summary

There are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.

Background

Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis.

Objective

Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma.

Methods

Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing.

Results

Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P<0.001; SAGE II: 235.99 vs. 223.07, P<0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes.

Conclusions

We observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group.