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1.  Validation of Parental Reports of Asthma Trajectory, Burden and Risk Using the Pediatric Asthma Control and Communication Instrument 
Despite a growing interest, few pediatric asthma questionnaires assess multiple dimensions of asthma morbidity, as recommended by national asthma guidelines, or use patient-reported outcomes.
To evaluate a questionnaire that measures multiple dimensions of parent-reported asthma morbidity (Direction, Bother and Risk).
Patients and Methods
We administered the Pediatric Asthma Control and Communication Instrument (PACCI) and assessed asthma control (PACCI Control), quality of life , and lung function among children presenting for routine asthma care. The PACCI was evaluated for discriminative validity.
317 children participated (mean age 8.2 years; 58% male; 44% African American). As parent-reported PACCI Direction changed from “better” to “worse”, we observed poorer asthma control (p<0.001), mean PACQLQ scores (p<0.001) and FEV1% (p = 0.025). Linear regression showed that for each change in PACCI Direction, the mean PACQLQ score decreased by −0.6 (95% CI: −0.8, −0.4). As parent-reported PACCI Bother changed from “not bothered” to “very bothered”, we observed poorer asthma control (p<0.001) and mean PACQLQ scores (p<0.001). Linear regression showed that for each change in PACCI Bother category, the mean PACQLQ score decreased by −1.1 (95% CI: −1.3, −0.9). Any reported PACCI Risk event (ED visit, hospitalization or use of an oral steroid) was associated with poorer asthma control (p<0.05) and PACQLQ scores (p<0.01).
PACCI Direction, Bother and Risk are valid measures of parent-reported outcomes and show good discriminative validity. The PACCI is a simple clinical tool to assess multiple dimensions of parent-reported asthma morbidity, in addition to risk and control.
PMCID: PMC4361408  PMID: 24607047
risk; children; burden; trajectory; survey; validation; PACCI; patient-reported outcomes
2.  The Pediatric Asthma Control and Communication Instrument asthma questionnaire: For use in diverse children of all ages 
National Institutes of Health asthma guidelines recommend questionnaires to assess asthma control, but these questionnaires are not useable across the entire pediatric age spectrum and have not been validated among significant numbers of minority or Spanish-speaking children.
We sought to evaluate a questionnaire designed to assess asthma control across a broad age range of minority and Spanish-speaking children cared for in an outpatient setting.
Between July 1, 2007, and September 30, 2010, we collected information using the Pediatric Asthma Control and Communication Instrument (PACCI), the Asthma Control Test (ACT; or the childhood ACT for children 4–11 years old), the Pediatric Asthma Caregiver Quality of Life Questionnaire, and lung function and clinicians’ ratings of asthma status among a population of children presenting for routine asthma specialist care. The PACCI measure of asthma control was validated by evaluating accuracy, internal reliability, and concurrent, discriminative, and known-groups validity.
We collected information on 265 English- and 52 Spanish-speaking children (mean age, 8.2 years; 58% male; 44% African American). Across all age groups and in both languages, PACCI control showed good internal reliability and strong concurrent, discriminative, and known-groups validity with ACT and Pediatric Asthma Caregiver Quality of Life Questionnaire scores and clinicians’ ratings of asthma control. The accuracy of the PACCI in classifying children with uncontrolled asthma was good (area under the curve, 0.83; 95% CI, 0.79–0.88).
The PACCI accurately measures asthma control in English- and Spanish-speaking children. The PACCI should be useful to clinicians to assess and classify asthma according to National Institutes of Health asthma guidelines.
PMCID: PMC4297654  PMID: 23434285
Impairment; control; children; assessment; accuracy; survey; validation; Pediatric Asthma Control and Communication Instrument; Spanish
3.  Socioeconomic Status and Childhood Asthma in Urban Minority Youths. The GALA II and SAGE II Studies 
Rationale: The burden of asthma is highest among socioeconomically disadvantaged populations; however, its impact is differentially distributed among racial and ethnic groups.
Objectives: To assess the collective effect of maternal educational attainment, annual household income, and insurance type on childhood asthma among minority, urban youth.
Methods: We included Mexican American (n = 485), other Latino (n = 217), and African American (n = 1,141) children (aged 8–21 yr) with and without asthma from the San Francisco Bay Area. An index was derived from maternal educational attainment, annual household income, and insurance type to assess the collective effect of socioeconomic status on predicting asthma. Logistic regression stratified by racial and ethnic group was used to estimate adjusted odds ratios (aOR) and their 95% confidence intervals (CI). We further examined whether acculturation explained the socioeconomic-asthma association in our Latino population.
Measurements and Main Results: In the adjusted analyses, African American children had 23% greater odds of asthma with each decrease in the socioeconomic index (aOR, 1.23; 95% CI, 1.09–1.38). Conversely, Mexican American children have 17% reduced odds of asthma with each decrease in the socioeconomic index (aOR, 0.83; 95% CI, 0.72–0.96) and this relationship was not fully explained by acculturation. This association was not observed in the other Latino group.
Conclusions: Socioeconomic status plays an important role in predicting asthma, but has different effects depending on race and ethnicity. Further steps are necessary to better understand the risk factors through which socioeconomic status could operate in these populations to prevent asthma.
PMCID: PMC3863734  PMID: 24050698
asthma; health status disparities; minority health; educational status; poverty
4.  Factors associated with degree of atopy in Latino children in a nationwide pediatric sample: The GALA II Study 
Atopy varies by ethnicity even within Latino groups. This variation may be due to environmental, socio-cultural or genetic factors.
To examine risk factors for atopy within a nationwide study of U.S. Latino children with and without asthma.
Aeroallergen skin test repsonse was analyzed in 1830 US latino subjects. Key determinants of atopy included: country / region of origin, generation in the U.S., acculturation, genetic ancestry and site to which individuals migrated. Serial multivariate zero inflated negative binomial regressions, stratified by asthma status, examined the association of each key determinant variable with the number of positive skin tests. In addition, the independent effect of each key variable was determined by including all key variables in the final models.
In baseline analyses, African ancestry was associated with 3 times as many positive skin tests in participants with asthma (95% CI:1.62–5.57) and 3.26 times as many positive skin tests in control participants (95% CI: 1.02–10.39). Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, Puerto Rican [exp(β) (95%CI): 1.31(1.02–1.69)] and mixed ethnicity [exp(β) (95%CI):1.27(1.03–1.56)] asthmatics had a greater probability of positive skin tests compared to Mexican asthmatics. Ancestry associations were abrogated by recruitment site, but not region of origin.
Puerto Rican ethnicity and mixed origin were associated with degree of atopy within U.S. Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization.
PMCID: PMC3788073  PMID: 23684070
Latino; atopy; region of origin; genetic ancestry; immigration; skin test; aeroallergen
5.  Whole-Genome Sequencing of Individuals from a Founder Population Identifies Candidate Genes for Asthma 
PLoS ONE  2014;9(8):e104396.
Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow-up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS.
PMCID: PMC4130548  PMID: 25116239
6.  Early-Life Air Pollution and Asthma Risk in Minority Children. The GALA II and SAGE II Studies 
Rationale: Air pollution is a known asthma trigger and has been associated with short-term asthma symptoms, airway inflammation, decreased lung function, and reduced response to asthma rescue medications.
Objectives: To assess a causal relationship between air pollution and childhood asthma using data that address temporality by estimating air pollution exposures before the development of asthma and to establish the generalizability of the association by studying diverse racial/ethnic populations in different geographic regions.
Methods: This study included Latino (n = 3,343) and African American (n = 977) participants with and without asthma from five urban regions in the mainland United States and Puerto Rico. Residential history and data from local ambient air monitoring stations were used to estimate average annual exposure to five air pollutants: ozone, nitrogen dioxide (NO2), sulfur dioxide, particulate matter not greater than 10 μm in diameter, and particulate matter not greater than 2.5 μm in diameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthma diagnosis. A random-effects model was used to combine the region-specific effects and generate summary odds ratios for each pollutant.
Measurements and Main Results: After adjustment for confounders, a 5-ppb increase in average NO2 during the first year of life was associated with an odds ratio of 1.17 for physician-diagnosed asthma (95% confidence interval, 1.04–1.31).
Conclusions: Early-life NO2 exposure is associated with childhood asthma in Latinos and African Americans. These results add to a growing body of evidence that traffic-related pollutants may be causally related to childhood asthma.
PMCID: PMC3778732  PMID: 23750510
air pollution; minority; children; asthma
7.  Childhood Obesity and Asthma Control in the GALA II and SAGE II Studies 
Rationale: Obesity is associated with increased asthma morbidity, lower drug responsiveness to inhaled corticosteroids, and worse asthma control. However, most prior investigations on obesity and asthma control have not focused on pediatric populations, considered environmental exposures, or included minority children.
Objectives: To examine the association between body mass index categories and asthma control among boys and girls; and whether these associations are modified by age and race/ethnicity.
Methods: Children and adolescents ages 8–19 years (n = 2,174) with asthma were recruited from the Genes-environments and Admixture in Latino Americans (GALA II) Study and the Study of African Americans, Asthma, Genes, and Environments (SAGE II). Ordinal logistic regression was used to estimate odds ratios (OR) and their confidence intervals (95% CI) for worse asthma control.
Measurements and Main Results: In adjusted analyses, boys who were obese had a 33% greater chance of having worse asthma control than their normal-weight counterparts (OR, 1.33; 95% CI, 1.04–1.71). However, for girls this association varied with race and ethnicity (P interaction = 0.008). When compared with their normal-weight counterparts, obese African American girls (OR, 0.65; 95% CI, 0.41–1.05) were more likely to have better controlled asthma, whereas Mexican American girls had a 1.91 (95% CI, 1.12–3.28) greater odds of worse asthma control.
Conclusions: Worse asthma control is uniformly associated with increased body mass index in boys. Among girls, the direction of this association varied with race/ethnicity.
PMCID: PMC3678111  PMID: 23392439
obesity; asthma control; race and ethnicity; age; sex
8.  Further Replication Studies of the EVE Consortium Meta-Analysis Identifies Two Asthma Risk Loci in European Americans 
Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk.
We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis.
We selected 3186 SNPs for replication based on the p-values from the EVE Consortium meta-analysis. These SNPs were genotyped in ethnically diverse replication samples from nine different studies, totaling to 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study and the resulting test statistics were combined in a meta-analysis.
Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined OR = 1.18; 95% CI 1.10 – 1.25) and rs9570077 (combined OR =1.20 95% CI 1.12–1.29) on chromosome 13q21. We could not replicate any additional associations in the African American or Latino individuals.
This extended replication study identified two additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latino individuals highlights the difficulty in replicating associations in admixed populations.
PMCID: PMC3666859  PMID: 23040885
Asthma; genetic risk factors; meta-analysis; KLK3
9.  Genetic variation in BAFF and asthma exacerbations among African American individuals 
Capsule Summary
A BAFF polymorphism is associated with asthma exacerbations and serum BAFF levels. BAFF expression in vivo increases in natural rhinovirus infection. BAFF may play a role in airway antiviral immunity and impact asthma exacerbation rates.
PMCID: PMC3520130  PMID: 22728080
BAFF; B-cell activating factor; tumor necrosis factor ligand superfamily; asthma; asthma exacerbations; genetics
10.  The impact of secondhand smoke on asthma control among Black and Latino children 
Among people with asthma, the clinical impact and relative contribution of maternal smoking during pregnancy (in utero smoking) and current secondhand smoke exposure on asthma control is poorly documented, and there is a paucity of research involving minority populations.
To examine the association between poor asthma control and in utero smoking and current secondhand smoke exposure among Latino and Black children with asthma.
Case-only analysis of 2 multi-center case-control studies conducted from 2008–2010 using similar protocols. We recruited 2,481 Latinos and Blacks with asthma (ages 8–17) from the mainland United States and Puerto Rico. Ordinal logistic regression was used to estimate the effect of in utero smoking and current secondhand smoke exposures on National Heart Lung and Blood Institute-defined asthma control.
Poor asthma control among children 8–17 years of age was independently associated with in utero smoking (odds ratio; 95% confidence interval = 1.5; 1.1–2.0). In utero smoking via the mother was also associated with secondary asthma outcomes, including early onset asthma (1.7; 1.1–2.4), daytime symptoms (1.6; 1.1–2.1), and asthma-related limitation of activities (1.6; 1.2–2.2).
Maternal smoking while in utero is associated with poor asthma control in Black and Latino subjects assessed at 8–17 years of age.
PMCID: PMC3367092  PMID: 22552109
Secondhand smoke; prenatal exposure delayed effects; asthma; health status disparities
11.  Admixture-Matched Case-Control Study: A Practical Approach for Genetic Association Studies in Admixed Populations 
Human genetics  2005;118(5):626-639.
Case-control genetic association studies in admixed populations are known to be susceptible to genetic confounding due to population stratification. The transmission/disequilibrium test (TDT) approach can avoid this problem. However, the TDT is expensive and impractical for late- onset diseases. Case-control study designs, in which cases and controls are matched by admixture, can be an appealing and suitable alternative for genetic association studies in admixed populations. In this study, we applied this matching strategy when recruiting our African American participants in the Study of African American, Asthma, Genes and Environments (SAGE). Group admixture in this cohort consists of 83% African ancestry and 17% European ancestry, which was consistent with reports from other studies. By carrying out several complementary analyses, our results show that there is substructure in the cohort, but that the admixture distributions are almost identical in cases and controls, and also in cases only. We performed association tests for asthma-related traits with ancestry, and only found that FEV1, a measure for baseline pulmonary function, was associated with ancestry after adjusting for socio-economic and environmental risk factors (P = 0.01). We did not observe an excess of type I error rate in our association tests for ancestry informative markers (AIMs) and asthma-related phenotypes when ancestry was not adjusted in the analyses. Furthermore, using the association tests between genetic variants in a known asthma candidate gene, β2 adrenergic receptor (β2AR) and ΔFEF25-75, an asthma-related phenotype, as an example, we demonstrated population stratification was not a confounder in our genetic association. Our present work demonstrates that admixture-matched case-control strategies can efficiently control for population stratification confounding in admixed populations.
PMCID: PMC3478103  PMID: 16273390
12.  Ethnic Variability in Persistent Asthma After In Utero Tobacco Exposure 
Pediatrics  2011;128(3):e623-e630.
The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent.
To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children.
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. The effect of in utero tobacco smoke exposure on the development of persistent asthma and related clinical outcomes was evaluated by logistic regression.
Children with persistent asthma had a higher odds of exposure to in utero tobacco smoke, but not current tobacco smoke, than did children with intermittent asthma (odds ratio [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years of life did not alter this association. Furthermore, there were higher odds of in utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR: 2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency department visits (OR: 3.85; P = .015) within the year.
Exposure to tobacco smoke in utero was significantly associated with persistent asthma among Mexican, Puerto Rican, and black children compared with those with intermittent asthma. These results suggest that smoking cessation during pregnancy may lead to a decrease in the incidence of persistent asthma in these populations.
PMCID: PMC3164096  PMID: 21859918
asthma; tobacco; Latino; African American; pregnancy
13.  ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos 
Understanding the effects of interactions between multiple genes and asthma medications may aid in the understanding of the heterogeneous response to asthma therapies.
To identify modulating effects of ALOX5AP and LTA4H gene polymorphisms on the drug-drug interaction between leukotriene modifiers and albuterol in Mexicans and Puerto Ricans.
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 was analyzed between leukotriene modifier users and non-users.
In heterozygotes and homozygotes for the minor allele at LTA4H SNP rs2540491 and heterozygotes for the major allele at LTA4H SNP rs2540487, leukotriene modifier use was associated with a clinically significant increase in percent change in forced expiratory volume in 1 second (FEV1) after albuterol administration of 7.10% (p=0.002), 10.06% (p=0.001), and 10.03% (p<0.001), respectively. Presence of the major allele at ALOX5AP SNP rs10507391 or the minor allele at ALOX5AP SNP rs9551963 augmented this response. When stratified by ethnicity, these findings held true for Puerto Ricans, but not Mexicans.
LTA4H and ALOX5AP gene polymorphisms modify the augmentation of bronchodilator responsiveness by leukotriene modifiers in Puerto Ricans but not Mexicans with asthma.
PMCID: PMC2950217  PMID: 20810156
asthma; leukotriene; leukotriene modifier; Latino; albuterol; drug responsiveness; association study; genetic polymorphism
14.  GSNO Reductase and β2 Adrenergic Receptor Gene-gene Interaction: Bronchodilator Responsiveness to Albuterol 
Pharmacogenetics and genomics  2010;20(6):351-358.
Short-acting inhaled β2-agonists such as albuterol are used for bronchodilation and are the mainstay of asthma treatment worldwide. There is significant variation in bronchodilator responsiveness to albuterol not only between individuals but also across racial/ethnic groups. The β2-adrenergic receptor (β2AR) is the target for β2-agonist drugs. The enzyme S-nitrosoglutathione reductase (GSNOR), which regulates levels of the endogenous bronchodilator S-nitrosoglutathione, has been shown to modulate the response to β2-agonists.
We hypothesized that there are pharmacogenetic interactions between GSNOR and β2AR gene variants which are associated with variable response to albuterol.
We performed family-based analyses to test for association between GSNOR gene variants and asthma and related phenotypes in 609 Puerto Rican and Mexican families with asthma. In addition, we tested these subjects for pharmacogenetic interaction between GSNOR and β2AR gene variants and responsiveness to albuterol using linear regression. Cell transfection experiments were performed to test the potential effect of the GSNOR gene variants.
Among Puerto Ricans, several GSNOR SNPs and a haplotype in the 3′UTR were significantly associated with increased risk for asthma and lower bronchodilator responsiveness (p = 0.04 to 0.007). The GSNOR risk haplotype affects expression of GSNOR mRNA and protein, suggesting a gain of function. Furthermore, gene-gene interaction analysis provided evidence of pharmacogenetic interaction between GSNOR and β2AR gene variants and the response to albuterol in Puerto Rican (p = 0.03), Mexican (p = 0.15) and combined Puerto Rican and Mexican asthmatics (p = 0.003). Specifically, GSNOR+17059*β2AR+46 genotype combinations (TG+GG*AG and TG+GG*GG) were associated with lower bronchodilator response.
Genotyping of GSNOR and β2AR genes may be a useful in identifying Latino subjects, who might benefit from adjuvant therapy for refractory asthma.
PMCID: PMC2883564  PMID: 20335826
Asthma; Bronchodilator responsiveness; GSNO Reductase; β2-Adrenergic Receptor; Latinos; Gene-gene interaction; Polymorphisms; Pharmacogenetics
15.  Genetic ancestry modifies pharmacogenetic gene–gene interaction for asthma 
Pharmacogenetics and genomics  2009;19(7):489-496.
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. Therefore, we reasoned that interactions between the IL6 and IL6R genes might be associated with bronchodilator drug responsiveness to albuterol in asthmatic patients.
Four functional IL6 single nucleotide polymorphisms (SNPs) and a nonsynonymous IL6R SNP were genotyped in 700 Mexican and Puerto Rican asthma families and in 443 African-American asthma cases and controls. Both family-based association tests and linear regression models were used to assess the association between individual SNPs and haplotypes with bronchodilator response. Gene–gene interactions were tested by using multiple linear regression analyses.
No single SNP was consistently associated with drug response in all the three populations. However, on the gene level, we found a consistent IL6 and IL6R pharmacogenetic interaction in the three populations. This pharmacogenetic gene–gene interaction was contextual and dependent upon ancestry (racial background). This interaction resulted in higher drug response to albuterol in Latinos, but lower drug response in African-Americans. Herein, we show that there is an effect modification by ancestry on bronchodilator responsiveness to albuterol.
Genetic variants in the IL6 and IL6R genes act synergistically to modify the bronchodilator drug responsiveness in asthma and this pharmacogenetic interaction is modified by the genetic ancestry.
PMCID: PMC2768127  PMID: 19503017
asthma genetics; African-Americans; ancestry; effect modification; gene–gene interaction; IL6; IL6 receptor; latinos
16.  Role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos 
Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of ALOX5AP and LTA4H in asthma have been inconclusive.
To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans.
The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single-nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analyzed for associations with asthma and asthma-related phenotypes in 687 parent-child trios of Mexican and Puerto Rican origin.
In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos (P = 0.007 and 0.05, respectively). Among Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (OR = 0.78, P = 0.02) and baseline lung function (P = 0.018) in Puerto Ricans. A gene-gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), (P = 0.003, in the combined sample).
Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations.
PMCID: PMC2866051  PMID: 20067482
Asthma; Leukotriene; Latino populations; Association study
17.  Ancestry-related assortative mating in Latino populations 
Genome Biology  2009;10(11):R132.
Examination of ancestry-informative genetic markers shows that Puerto Rican and Mexican populations have shown strong assortative mating that continues to this day.
While spouse correlations have been documented for numerous traits, no prior studies have assessed assortative mating for genetic ancestry in admixed populations.
Using 104 ancestry informative markers, we examined spouse correlations in genetic ancestry for Mexican spouse pairs recruited from Mexico City and the San Francisco Bay Area, and Puerto Rican spouse pairs recruited from Puerto Rico and New York City. In the Mexican pairs, we found strong spouse correlations for European and Native American ancestry, but no correlation in African ancestry. In the Puerto Rican pairs, we found significant spouse correlations for African ancestry and European ancestry but not Native American ancestry. Correlations were not attributable to variation in socioeconomic status or geographic heterogeneity. Past evidence of spouse correlation was also seen in the strong evidence of linkage disequilibrium between unlinked markers, which was accounted for in regression analysis by ancestral allele frequency difference at the pair of markers (European versus Native American for Mexicans, European versus African for Puerto Ricans). We also observed an excess of homozygosity at individual markers within the spouses, but this provided weaker evidence, as expected, of spouse correlation. Ancestry variance is predicted to decline in each generation, but less so under assortative mating. We used the current observed variances of ancestry to infer even stronger patterns of spouse ancestry correlation in previous generations.
Assortative mating related to genetic ancestry persists in Latino populations to the current day, and has impacted on the genomic structure in these populations.
PMCID: PMC3091325  PMID: 19930545
18.  An african-specific functional polymorphism in KCNMB1 shows sex-specific association with asthma severity 
Human Molecular Genetics  2008;17(17):2681-2690.
A highly heritable and reproducible measure of asthma severity is baseline pulmonary function. Pulmonary function is largely determined by airway smooth muscle (ASM) tone and contractility. The large conductance, voltage and calcium-activated potassium (BK) channel negatively regulates smooth muscle tone and contraction in ASM. The modulatory subunit of BK channels, the β1-subunit, is critical for proper activation of BK channels in smooth muscle and has shown sex hormone specific regulation. We hypothesized that KCNMB1 genetic variants in African Americans may underlie differences in bronchial smooth muscle tone and thus pulmonary function, possibly in a sex-specific manner. Through resequencing of the KCNMB1 gene we identified several common variants including a novel African-specific coding polymorphism (C818T, R140W). The C818T SNP and four other KCNMB1 variants were genotyped in two independent groups of African American asthmatics (n = 509) and tested for association with the pulmonary function measure – forced expiratory volume (FEV1) % of predicted value. The 818T allele is associated with a clinically significant decline (−13%) in FEV1 in both cohorts of asthmatics among males but not females (Pcombined = 0.0003). Patch clamp electrophysiology studies of the BK channel expressed with the 140Trp variant of the β1-subunit demonstrated significantly reduced channel openings, predicted by the loss of pulmonary function observed. African American male asthmatics carrying the 818T allele (10% of population) are potentially at risk for greater airway obstruction and increased asthma morbidity. Female asthmatics may be insulated from the deleterious effects of the 818T allele by estrogen-mediated upregulation in BK channel activity.
PMCID: PMC2733805  PMID: 18535015
19.  The Use of Telemedicine Access to Schools to Facilitate Expert Assessment of Children with Asthma 
Research has shown that access to an asthma specialist improves asthma outcomes. We hypothesized that we could improve access to expert asthma care through a telemedicine link between an asthma specialist and a school-based asthma program. We conducted a prospective cohort study in 3 urban schools to ascertain the feasibility of using an asthma-focused telemedicine solution. Each subject was seen by an asthma expert at 0, 8, and 32 weeks. The assessment and recommendations for care were sent to the primary care physician (PCP) and parents were told to contact their physician for follow-up care. Eighty three subjects participated in the study. Subjects experienced improvement (P < .05) in family social activities and the number of asthma attacks. Ninety four percent of subjects rated the program as good or excellent. This study demonstrates the feasibility and acceptance of a school-based asthma program using a telemedicine link to an asthma specialist.
PMCID: PMC2271044  PMID: 18369409

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