African ancestry, early life exposures, and respiratory morbidity in early childhood.

Background: Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors.

Objective: To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures.

Methods: We studied 1034 children in an urban, multi-racial, prospective birth cohort.

Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid nonadherence.

Background: Asthma is an inflammatory condition often punctuated by episodic symptomatic worsening, and accordingly, patients with asthma might have waxing and waning adherence to controller therapy.

Objective: We sought to measure changes in inhaled corticosteroid (ICS) adherence over time and to estimate the effect of this changing pattern of use on asthma exacerbations.

Methods: ICS adherence was estimated from electronic prescription and fill information for 298 participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity.

Ethnic variability in persistent asthma after in utero tobacco exposure.

Background: The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent.

Objective: To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children.

Patients And Methods: There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview.

Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.

Mutations in genes that encode components of the sarcomere are well established as the cause of hypertrophic and dilated cardiomyopathies. Sarcomere genes, however, are increasingly being associated with other cardiomyopathies. One phenotype more recently recognized as a disease of the sarcomere is restrictive cardiomyopathy (RCM).

Identification of ATPAF1 as a novel candidate gene for asthma in children.

Background: Asthma is a common disease of children with a complex genetic origin. Understanding the genetic basis of asthma susceptibility will allow disease prediction and risk stratification.

Objective: We sought to identify asthma susceptibility genes in children.

Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations.

Background: Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity.

Objectives: More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performed.

History shaped the geographic distribution of genomic admixture on the island of Puerto Rico.

Contemporary genetic variation among Latin Americans human groups reflects population migrations shaped by complex historical, social and economic factors. Consequently, admixture patterns may vary by geographic regions ranging from countries to neighborhoods. We examined the geographic variation of admixture across the island of Puerto Rico and the degree to which it could be explained by historic and social events.

Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group.

In January 2009, the National Heart, Lung, and Blood Institute convened a 28-member multidisciplinary Working Group to update the recommendations of a 2004 National Heart, Lung, and Blood Institute Working Group focused on Guidelines to the Return of Genetic Research Results. Changes in the genetic and societal landscape over the intervening 5 years raise multiple questions and challenges. The group noted the complex issues arising from the fact that technological and bioinformatic progress has made it possible to obtain considerable information on individuals that would not have been possible a decade ago.

Perisciatic infusion of ropivacaine and analgesia after hallux valgus repair.

Background: Moderate to severe pain after hallux valgus repair can be successfully treated with a continuous popliteal sciatic nerve block in ambulatory patients. Different anesthesiologists use various infusion rates for this purpose. The aim of this study was to compare the analgesic efficacy of two infusion rates of ropivacaine 2 mg/ml: 5 and 8 ml/h.

Factors predicting inhaled corticosteroid responsiveness in African American patients with asthma.

Background: African American patients disproportionately experience uncontrolled asthma. Treatment with an inhaled corticosteroid (ICS) is considered first-line therapy for persistent asthma.

Objective: We sought to determine the degree to which African American patients respond to ICS medication and whether the level of response is influenced by other factors, including genetic ancestry.

ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos.

Background: Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies.

Objective: To identify modulating effects of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans.

Methods: In a cross-sectional study of 293 Mexicans and 356 Puerto Ricans with asthma, ALOX5AP and LTA4H genes were sequenced, and interactions between gene polymorphisms and bronchodilator responsiveness to albuterol were compared between leukotriene modifier users and nonusers.

Dual-specificity phosphatase 1 as a pharmacogenetic modifier of inhaled steroid response among asthmatic patients.

Background: Inhaled corticosteroids (ICSs) are considered first-line treatment for persistent asthma, yet there is significant variability in treatment response. Dual-specificity phosphatase 1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids.

Objective: We sought to determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment.

Genetic ancestry in lung-function predictions.

Background: Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American.

Methods: We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression.

The 1000 Genomes Project: new opportunities for research and social challenges.

The 1000 Genomes Project, an international collaboration, is sequencing the whole genome of approximately 2,000 individuals from different worldwide populations. The central goal of this project is to describe most of the genetic variation that occurs at a population frequency greater than 1%. The results of this project will allow scientists to identify genetic variation at an unprecedented degree of resolution and will also help improve the imputation methods for determining unobserved genetic variants that are not represented on current genotyping arrays.

A genome-wide association study on African-ancestry populations for asthma.

Background: Asthma is a complex disease characterized by striking ethnic disparities not explained entirely by environmental, social, cultural, or economic factors. Of the limited genetic studies performed on populations of African descent, notable differences in susceptibility allele frequencies have been observed.

Objectives: We sought to test the hypothesis that some genes might contribute to the profound disparities in asthma.

Institutional Profile: The University of California Pharmacogenomics Center: at the interface of genomics, biological mechanisms and drug therapy.

The Pharmacogenomics Center of the University of California, San Francisco (CA, USA) fosters research and educational activities focused on the genomic basis for variation in drug response. Investigators in the Center conduct multidisciplinary and multicenter research on a diverse array of clinically used drugs with the goal of understanding the genetic factors that contribute to variation in therapeutic and adverse drug response. The Center houses the large NIH-supported Pharmacogenomics of Membrane Transporters Project, which is a leader in understanding genetic variation in membrane transporters that are important in clinical drug response.

Recent advances of genetic ancestry testing in biomedical research and direct to consumer testing.

In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response.

Augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Rican and Mexican children.

Background: Ethnic-specific interactions between different asthma medications are not well described.

Objective: To determine whether the use of leukotriene modifiers is associated with the magnitude of bronchodilator responsiveness among Mexican American and Puerto Rican children with persistent asthma.

Methods: A cross-sectional study of 84 Mexican American and 192 Puerto Rican children, with persistent asthma who were aged 8 to 16 years.

Birthplace and mortality among insured Latinos: the paradox revisited.

Objectives: We investigated the Latino paradox in a managed care setting and examined the role of birthplace.

Methods: We evaluated 133,155 non-Latino Whites and 5,237 Latinos (36% born in the United States, 34% in Central and South America, 21% in Mexico, and 8% in the Caribbean Islands) who were enrolled in an integrated healthcare delivery system in northern California. Baseline data were from 1964-1973, and the median followup was 34 years.

Genetic ancestry modifies pharmacogenetic gene-gene interaction for asthma.

Objective: A recent admixture mapping analysis identified interleukin 6 (IL6) and IL6 receptor (IL6R) as candidate genes for inflammatory diseases. In the airways during allergic inflammation, IL6 signaling controls the production of proinflammatory and anti-inflammatory factors. In addition, albuterol, a commonly prescribed asthma therapy, has been shown to influence IL6 gene expression.