ORCID Profile
0000-0001-7475-2035
Current Organisations
University of California, San Francisco
,
University of California, Berkeley
,
Stanford University School of Medicine
,
San Francisco State University
,
Harvard School of Public Health
,
Brigham and Women's Hospital
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 29-10-2021
DOI: 10.1126/SCIIMMUNOL.ABH0707
Abstract: Type 2 immune development depends on MARCH1-mediated turnover of MHCII and CD86 by lymph node–resident dendritic cells.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 06-10-2020
DOI: 10.1101/2020.10.05.20206847
Abstract: Leukotrienes play a central pathophysiological role in both pediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. To test the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically erse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). In iduals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against in iduals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset in iduals from European ancestry demonstrated the risk of experiencing asthma exacerbations in the G allele carriers’ group (AG or GG), despite montelukast treatment, was increased (odds-ratio=3.27, 95%confidence interval: 0.98–10.93, I2=69%, p=0.05) compared to those in the AA group. When meta-analyzing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR=1.69, 95% CI: 0.56-5.09, I2=84.81%, p=0.35). Our study demonstrates that genetic variation in LTA4H , together with timing of asthma onset, may contribute to variability in montelukast response. Europeans in iduals with early-onset (≤18y) carrying the rs2660845 G allele have increased risk of exacerbation under montelukast treatment, presumably due to the up-regulation of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast.
Publisher: Wiley
Date: 09-07-2018
DOI: 10.1111/ALL.13499
Publisher: Wiley
Date: 06-2022
DOI: 10.1111/PAI.13802
Abstract: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi‐ancestry meta‐analysis of genome‐wide association studies (meta‐GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across erse populations and to assess their functional role in regulating DNA methylation and gene expression. A meta‐GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants ( p ≤ 5 × 10 −5 ) were assessed for replication in 36,477 European and 1078 non‐European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. One hundred and twenty‐six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule‐1/exostosin like glycosyltransferase‐2 ( VCAM1 / EXTL2 ) (discovery: odds ratio (OR T allele ) = 0.82, p = 9.05 × 10 −6 and replication: OR T allele = 0.89, p = 5.35 × 10 −3 ) and rs943126 from pantothenate kinase 1 ( PANK1 ) (discovery: OR C allele = 0.85, p = 3.10 × 10 −5 and replication: OR C allele = 0.89, p = 1.30 × 10 −2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. This multi‐ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Esteban Burchard.