Differential endothelial cell gene expression by African Americans <Emphasis Type="Italic">versus</Emphasis>Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer

Background  

Health disparities and the high prevalence of cardiovascular disease continue to be perplexing worldwide health challenges. This study addresses the possibility that genetic differences affecting the biology of the vascular endothelium could be a factor contributing to the increased burden of cardiovascular disease and cancer among African Americans (AA) compared to Caucasian Americans (CA).     

Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects

Background  

Betacellulin is a member of the epidermal growth factor family, expressed at the highest levels predominantly in the pancreas and thought to be involved in islet neogenesis and regeneration. Nonsynonymous coding variants were reported to be associated with type 2 diabetes in African American subjects. We tested the hypotheses that these previously identified variants were associated with type 2 diabetes in African Americans ascertained in Arkansas and that they altered insulin secretion in glucose tolerant African American subjects.     

Use of multivitamins,folic acid and herbal supplements among breast cancer survivors: the black women's health study

Background  

Complementary and alternative medicine (CAM) use, including herbals and multivitamin supplements, is quite common in the U.S., and has been shown to be highest in breast cancer survivors. However, limited data are currently available for CAM usage among African Americans. Thus, we sought to determine the prevalence of multivitamins, folic acid and herbal supplement usage in African American breast cancer survivors, and to compare the characteristics of users and nonusers.     

Central Serous Chorioretinopathy in African Americans at Wilmer Eye Institute

Objective

To evaluate the frequency of central serous chorioretinopathy (CSC) in African Americans/blacks within an academic center in a predominantly African American city, as the current belief is that CSC is rare in this population.

Lack of association between genetic polymorphisms within <Emphasis Type="Italic">DUSP12 -</Emphasis><Emphasis Type="Italic">ATF6</Emphasis>locus and glucose metabolism related traits in a Chinese population

Background  

Genome-wide linkage studies in multiple ethnic populations found chromosome 1q21-q25 was the strongest and most replicable linkage signal in the human chromosome. Studies in Pima Indian, Caucasians and African Americans identified several SNPs in DUSP12 and ATF6, located in chromosome 1q21-q23, were associated with type 2 diabetes.     

Comparison between the HCV IRES domain IV RNA structure and the Iron Responsive Element

Background  

Serum ferritin and hepatic iron concentrations are frequently elevated in patients who are chronically infected with the hepatitis C virus (HCV), and hepatic iron concentration has been used to predict response to interferon therapy, but these correlations are not well understood. The HCV genome contains an RNA structure resembling an iron responsive element (IRE) in its internal ribosome entry site (IRES) structural domain IV (dIV). An IRE is a stem loop structure used to control the expression of eukaryotic proteins involved in iron homeostasis by either inhibiting ribosomal binding or protecting the mRNA from nuclease degradation. The HCV structure, located within the binding site of the 40S ribosomal subunit, might function as an authentic IRE or by an IRE-like mechanism.     

In Vivo β-Adrenergic Receptor Responsiveness: Ethnic Differences in the Relationship with Symptoms of Depression and Fatigue

Background

Depressive symptoms and fatigue frequently overlap in clinical samples and the general population. The link of depressive symptoms and fatigue with increased risk of cardiovascular disease has been partly explained by shared biological mechanisms including sympathetic overactivity. Prolonged sympathetic overactivity downregulates the responsiveness of the β-adrenergic receptor (β-AR), a receptor that mediates several end-organ sympathetic responses.

Purpose

The authors studied whether depression and fatigue are related to reduced β-AR responsiveness within the human body (in vivo) in an ethnically diverse sample of African and Caucasian Americans.

Methods

The chronotropic₂₅ dose (CD₂₅) was used to determine in vivo β-AR responsiveness in 93 healthy participants. Psychometric measures included the Center of Epidemiological Studies-Depression Scale and the Multidimensional Fatigue Symptom Inventory.

Results

Hierarchical regression analyses (adjusted for age, gender, body mass index, blood pressure, smoking, and ethnicity) revealed that mental fatigue was significantly related to reduced β-AR responsiveness (i.e., higher CD₂₅ values) in the whole sample. Moderation analyses indicated significant ethnicity × depression/fatigue interactions. Depressive symptoms, total fatigue, emotional fatigue, mental fatigue, and physical fatigue were related to reduced β-AR responsiveness in Caucasian American but not in African Americans.

Conclusions

Our findings suggest that symptoms of depression and fatigue are related to decreased in vivo β-AR responsiveness in Caucasian Americans. The lack of this association in African Americans highlights the importance for considering ethnicity as a potential moderator in research focusing on associations between psychological variables and cardiovascular function.     

Effect of Age,Gender, and Sun Exposure on Ethnic Skin Photoaging: Evidence Gathered Using a New Photonumeric Scale

Background

African–Americans are less affected by photoaging than lighter skin individuals. Although scales for photoaging have been developed for Caucasians and Asians, no scale exists for African–Americans.

Insomnia Did Not Predict Incident Hypertension in Older Adults in the Cardiovascular Health Study

Study Objective:

We hypothesized that the sleep complaints of insomnia predict incident hypertension, particularly in African Americans. The purpose of this study was to analyze insomnia complaints as predictors of incident hypertension in the Cardiovascular Health Study (CHS), stratifying by gender and allowing for race and sleep variable interaction.

Design:

This is a prospective cohort study over a 6-year period of follow-up.

Setting:

This is a community-based study of participants in Forsyth County, North Carolina; Pittsburgh, Pennsylvania; Sacramento County, California; and Washington County, Maryland.

Participants:

The study analyzed data from 1419 older individuals (baseline mean age 73.4 ± 4.4 years) from the Cardiovascular Health Study who were not hypertensive at baseline.

Interventions:

none

Measurements:

We constructed relative risks of incident hypertension over a 6-year period for insomnia complaints singly and in combination.

Results:

Difficulty falling asleep, singly or in combination with other sleep complaints, predicted a statistically significant reduction of risk for incident hypertension for non-African American men in 6 years of follow-up. Insomnia complaints did not predict incident hypertension in 6 years of follow-up in women or in African Americans, although there may not have been enough power to show a significant association for African Americans.

Conclusions:

Insomnia did not predict hypertension in this older cohort which was free of hypertension at baseline. Difficulty falling asleep was associated with reduced risk of hypertension in non-African American men.

Citation:

Phillips B; Bůžková P; Enright P. Insomnia did not predict incident hypertension in older adults in the cardiovascular health study. SLEEP 2009;32(1):65-72.     

The status of clinical trials: Cause for concern

Background  

Americans see clinical research as important, with over 15 million American residents participating in NIH-sponsored studies in 2008 and growing yearly.     

Quantification of liver iron overload disease with laser ablation inductively coupled plasma mass spectrometry

Background

Hereditary hemochromatosis is the most frequent, identified, genetic disorder in Caucasians affecting about 1 in 1000 people of Northern European ancestry, where the associated genetic defect (homozygosity for the p.Cys282Tyr polymorphism in the HFE gene) has a prevalence of approximately 1:200. The disorder is characterized by excess iron stores in the body. Due to the incomplete disease penetrance of disease-associated genotype, genetic testing and accurate quantification of hepatic iron content by histological grading of stainable iron, quantitative chemical determination of iron, or imaging procedures are important in the evaluation and staging of hereditary hemochromatosis.

Methods

We here established novel laser ablation inductively coupled plasma mass spectrometry protocols for hepatic metal bio-imaging for diagnosis of iron overload.

Results

We demonstrate that these protocols are a significant asset in the diagnosis of iron overload allowing iron measurements and simultaneous determination of various other metals and metalloids with high sensitivity, spatial resolution, and quantification ability.

Conclusions

The simultaneous measurement of various metals and metalloids offers unique opportunities for deeper understanding of metal imbalances. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a highly powerful and sensitive technique for the analysis of a variety of solid samples with high spatial resolution. We conclude that this method is an important add-on to routine diagnosis of iron overload and associated hepatic metal dysbalances resulting thereof.

     

Protective effect of KCNH2 single nucleotide polymorphism K897T in LQTS families and identification of novel KCNQ1 and KCNH2 mutations

Background

In a previous study of the Hypertension Genetic Epidemiology Network (HyperGEN) we have shown that metabolic syndrome (MetS) risk factors were moderately and significantly associated with echocardiographic (ECHO) left ventricular (LV) phenotypes.

Methods

The study included 1,393 African Americans and 1,133 whites, stratified by type 2 diabetes mellitus (DM) status. Heritabilities of seven factor scores based on the analysis of 15 traits were sufficiently high to pursue QTL discovery in this follow-up study.

Results

Three of the QTLs discovered relate to combined MetS-ECHO factors of "blood pressure (BP)-LV wall thickness" on chromosome 3 at 225 cM with a 2.8 LOD score, on chromosome 20 at 2.1 cM with a 2.6 LOD score; and for "LV wall thickness" factor on chromosome 16 at 113.5 with a 2.6 LOD score in whites. The remaining QTLs include one for a "body mass index-insulin (BMI-INS)" factor with a LOD score of 3.9 on chromosome 2 located at 64.8 cM; one for the same factor on chromosome 12 at 91.4 cM with a 3.3 LOD score; one for a "BP" factor on chromosome 19 located at 67.8 cM with a 3.0 LOD score. A suggestive linkage was also found for "Lipids-INS" with a 2.7 LOD score located on chromosome 11 at 113.1 cM in African Americans. Of the above QTLs, the one on chromosome 12 for "BMI-INS" is replicated in both ethnicities, (with highest LOD scores in African Americans). In addition, the QTL for "LV wall thickness" on chromosome 16q24.2-q24.3 reached its local maximum LOD score at marker D16S402, which is positioned within the 5th intron of the cadherin 13 gene, implicated in heart and vascular remodeling.

Conclusion

Our previous study and this follow-up suggest gene loci for some crucial MetS and cardiac geometry risk factors that contribute to the risk of developing heart disease.     

Informed and patient-centered decision-making in the primary care visits of African Americans with depression

Objective

We examined the prevalence and extent of informed decision-making (IDM) and patient-centered decision-making (PCDM) in primary care visits of African Americans with depression.

Sequelae due to bacterial meningitis among African children: a systematic literature review

Background  

African children have some of the highest rates of bacterial meningitis in the world. Bacterial meningitis in Africa is associated with high case fatality and frequent neuropsychological sequelae. The objective of this study is to present a comprehensive review of data on bacterial meningitis sequelae in children from the African continent.     

Lipoprotein levels and cardiovascular risk in HIV-infected and uninfected Rwandan women

Background  

Lipoprotein profiles in HIV-infected African women have not been well described. We assessed associations of lipoprotein levels and cardiovascular risk with HIV-infection and CD4 count in Rwandan women.     

Genetic analysis of the GLUT10 glucose transporter (<Emphasis Type="Italic">SLC2A10</Emphasis>) polymorphisms in Caucasian American type 2 diabetes

Background  

GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans.     

Racial Discrimination Is Associated with a Measure of Red Blood Cell Oxidative Stress: A Potential Pathway for Racial Health Disparities

Background

There are racial health disparities in many conditions for which oxidative stress is hypothesized to be a precursor. These include cardiovascular disease, diabetes, and premature aging. Small clinical studies suggest that psychological stress may increase oxidative stress. However, confirmation of this association in epidemiological studies has been limited by homogenous populations and unmeasured potential confounders.

Purpose

We tested the cross-sectional association between self-reported racial discrimination and red blood cell (RBC) oxidative stress in a biracial, socioeconomically heterogeneous population with well-measured confounders.

Methods

We performed a cross-sectional analysis of a consecutive series of 629 participants enrolled in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Conducted by the National Institute on Aging Intramural Research Program, HANDLS is a prospective epidemiological study of a socioeconomically diverse cohort of 3,721 Whites and African Americans aged 30?C64?years. Racial discrimination was based on self-report. RBC oxidative stress was measured by fluorescent heme degradation products. Potential confounders were age, smoking status, obesity, and C-reactive protein.

Results

Participants had a mean age of 49?years (SD?=?9.27). In multivariable linear regression models, racial discrimination was significantly associated with RBC oxidative stress (Beta?=?0.55, P?<?0.05) after adjustment for age, smoking, C-reactive protein level, and obesity. When stratified by race, discrimination was not associated with RBC oxidative stress in Whites but was associated significantly for African Americans (Beta?=?0.36, P?<?0.05).

Conclusions

These findings suggest that there may be identifiable cellular pathways by which racial discrimination amplifies cardiovascular and other age-related disease risks.     

Rosai-Dorfman Disease: A previously unreported association with Sickle Cell Disease

Background  

Rosai-Dorfman Disease is an uncommon benign systemic histio-proliferative disease. This is the first time the disease, although more common in people of African descent, is described in association with Sickle cell disease.     

A draft framework for measuring progress towards the development of a national health information infrastructure

Background  

American public policy makers recently established the goal of providing the majority of Americans with electronic health records by 2014. This will require a National Health Information Infrastructure (NHII) that is far more complete than the one that is currently in its formative stage of development. We describe a conceptual framework to help measure progress toward that goal.     

Genetic predictors for acute experimental cold and heat pain sensitivity in humans

Background

The genetic contribution to pain sensitivity underlies a complex composite of parallel pain pathways, multiple mechanisms, and diverse inter‐individual pain experiences and expectations.

Methods

Variations for genes encoding receptors related to cold and heat sensation, such as transient receptor potential A subtype 1 (TRPA1), M subtype 8 (TRPM8), V subtype 1 (TRPV1), δ opioid receptor subtype 1 (OPRD1), catechol O‐methyltransferase (COMT), and fatty acid amide hydrolyase (FAAH), were investigated in four major ethnic populations.

Results

We defined 13 haplotype blocks in European Americans, seven blocks in African Americans, seven blocks in Hispanic subjects, and 11 blocks in Asian Americans. Further study in European American subjects found significant associations between short duration cold pain sensitivity and variations in TRPA1, COMT, and FAAH in a gender dependent manner. Our observations demonstrate that genetic variations in TRPA1, COMT, and FAAH contribute gender specifically to individual variations in short duration cold pain sensitivity in a European American cohort.

Conclusions

The effects of TRPA1 variations on experimental short duration heat pain sensitivity may contribute to inter‐individual variation in pain sensitivity in humans.