Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity.

Abstract

BACKGROUND: The CD14 C-159T single nucleotide polymorphism (SNP) has been investigated widely as a candidate genetic locus in patients with allergic disease. There are conflicting results for the association of the CD14 C-159T SNP with total serum immunoglobulin E (IgE) levels and atopy. There are limited data regarding the association of the CD14 C-159T SNP in subjects of African ancestry. The aim of the study was to determine whether the C-159T SNP and other CD14 SNPs (C1188G, C1341T) were associated with total serum IgE levels and with allergy skin test results in nonatopic and atopic subjects; as well as in Caucasian and African American subjects. METHODS: A total of 291 participants, 18-40 years old, were screened to determine whether they were atopic and/or asthmatic. Analyses were performed to determine the association between CD14 C-159T, C1188G, or C1341T genotypes with serum IgE levels and with the number of positive skin tests among Caucasian or African American subjects. RESULTS: We found no significant association of serum total IgE level with CD14 C-159T, C1188G, or C1341T genotypes within nonatopic or atopic subjects. Subjects with CD14-159 T alleles had significantly more positive allergen skin tests than subjects without CD14-159 T alleles (P = 0.0388). There was a significant association between the CD14 1188 G allele, but not the CD14 1341 T allele, with the number of positive skin-test results in Caucasians, but not in African Americans. CONCLUSION: These results support a possible association between CD14 polymorphisms and atopy. CD14-159 T or CD14 1188 G alleles were associated with atopic disease. For subjects with CD14 1188 G alleles, the association with atopic disease was stronger in Caucasians compared to African Americans.

Department

Description

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Citation

Published Version (Please cite this version)

10.2147/jaa.s42695

Publication Info

Wang, Zongyao, John S Sundy, Catherine M Foss, Huiman X Barnhart, Scott M Palmer, Sallie D Allgood, Evan Trudeau, Katie M Alexander, et al. (2013). Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity. Journal of asthma and allergy, 6. pp. 81–92. 10.2147/jaa.s42695 Retrieved from https://hdl.handle.net/10161/21126.

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Scholars@Duke

Sundy

John Sargent Sundy

Adjunct Professor in the Department of Medicine

Research Theme

The focus of my research is on human-based translational studies and therapeutic trials of novel agents for inflammatory and immunologic diseases. My group has experience in mechanistic studies of environmental exposure in airway diseases; genetic analysis and gene expression studies using microarrays; airway challenge and assessment of response in the upper and lower airway and periphery; and therapeutic trials of experimental agents in Phases I-IV. Areas of focus include:

Asthma and Allergic Diseases

Research interests in asthma and allergic diseases focus upon human studies investigating the response to environmental endotoxin exposure. Using airway challenge with lipopolysaccharide and well characterized allergens, we investigate the genetic regulation of immunologic and inflammatory responses in the lung and in the periphery. This work is performed in collaboration with investigators with expertise in bench science and computational biology. In addition I participate in a number of multi-center research projects related to experimental therapeutics and genetic susceptibility to asthma and allergic diseases.

Rheumatologic Diseases

My primary research focus in rheumatologic diseases is on experimental therapeutics in chronic gout. Gout is the most common inflammatory arthritis in men, and the prevalence of disease is increasing in the population. We have led Phase I through III studies of pegloticase (PEGylated uricase) in subjects with treatment failure gout. We have initiated a new line of investigation that focuses upon IL-1 inhibition in the treatment of inflammation in acute and chronic gout.

Duke Clinical Research Institute - Multicenter Clinical Trials

I serve as the Director of Rheumatology and Allergy Research at the Duke Clinical Research Institute, a large academic research organization with expertise in the coordination of multi-center clinical trials and registries. Our objective is to develop a diverse portfolio of research registries and clinical trials in rheumatic and immunologic disease led by investigators at Duke. Currently our group is involved in programs in pediatric lupus, systemic onset JIA, gout, rheumatoid arthritis, and scleroderma.

Barnhart

Huiman Xie Barnhart

Professor of Biostatistics & Bioinformatics

My research interests include both statistical methodology and disease-specific clinical research biostatistics. My statistical research areas include methods for outcomes, endpoints, estimands, assessing reliability/agreement between methods or raters, evaluating performance of new medical diagnostic tests, and methods for design of clinical trials. My collaborative research include the following clinical areas: liver injury, cardiovascular imaging, radiology imaging, cardiovascular disease, renal disease, reproductive medicine, Parkinson disease, and aging.

Palmer

Scott Michael Palmer

Donald F. Fortin, M.D. Distinguished Professor of Medicine

Dr. Palmer leads a successful program of clinical, basic and translational research in lung transplantation, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans (BO) and other lung diseases. He directs the Medicine Plus Therapeutic Area at the Duke Clinical Research Institute (DCRI) and serves as Vice Chair for Research in the Department of Medicine. He is also the Director of Clinical Research, Duke Transplant Center.

Dr. Palmer has over 250 peer reviewed publications, received numerous awards, including election into the American Society for Clinical Investigation (ASCI) in 2012, chaired many sessions at national and international meetings, serves regularly on NIH study sections, and is on the editorial board of many prominent journals. He is a dedicated mentor to trainees and junior faculty, having personally mentored over 40 pre-and post-doctoral trainees, many of whom are now engaged in their own successful research careers. He is multiple PI on two Duke R38 awards supporting dedicated resident research, and multiple PI for a Duke Pulmonary T32 training program, all reflecting his deep commitment to support and train the next generation of physician investigators. He has received continuous NIH funding since 2002.

His scientific accomplishments include high impact studies that have demonstrated the importance of innate immunity in transplant rejection, a clinical trial that improved cytomegalovirus (CMV) prevention after lung transplantation, and work that identified rare protein coding exome variants that contribute to the development of IPF.  In addition to these studies he has led numerous multicenter studies, registries and clinical trials.  His program of translational research focuses on the use of human tissue and samples in studying pulmonary transplant rejection, and the use of human airway cells epithelial cells in the study of bronchiolitis obliterans including in the transplant and occupational setting. Recent work has employed single cell RNAseq to discover novel cell types and mechanisms involved in lung disease and transplant rejection.  


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