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Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy

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Abstract

Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4–17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR) = 1.42, 95% confidence interval (CI) = 1.08–1.87 for one copy; RR (95%CI) = 1.95 (1.36–2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09–1.98) for one and 2.00 (1.38–2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR = 1.48, 95% CI = 1.11–1.95 for one copy; RR = 1.77, 95% CI = 1.22–2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders.

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Abbreviations

FDR:

False discovery rate

FEV1 :

Forced expiratory volume in 1 s

OR:

Odds ratio

RR:

Relative risk

SNP:

Single nucleotide polymorphism

TDT:

Transmission disequilibrium test

TGFB1:

Transforming growth factor, beta-1

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Acknowledgments

This study was supported by the Division of Intramural Research, National Institute of Environmental Health Sciences (Z01 ES49019), National Institutes of Health, Department of Health and Human Services, USA, and the National Council of Science and Technology (Grant 26206-M), Mexico. Dr. Romieu is supported by the National Center for Environmental Health at the Centers for Disease Control, USA. The authors would like to acknowledge the children and parents who participated in this study; Stephan Chanock, MD, National Cancer Institute, NIH, DHHS, for determination of short tandem repeats for parentage testing; Grace Chiu, Ph.D. (Westat, Research Triangle Park, NC) for data management and analyses; and Susan Baker, Sarah Lein and Sheri McReynolds (Social and Scientific Systems, Inc.; Research Triangle Park, NC) for specimen handling and database management. The authors wish to thank Dulce Ramirez for participation in the fieldwork and Drs. Clarice Weinberg and John Sundy for critical review of the manuscript.

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Authors and Affiliations

  1. Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

    Huiling Li, Hao Wu & Stephanie J. London

  2. Epidemiology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, MD A3-05, Research Triangle Park, NC, 27709, USA

    Stephanie J. London

  3. National Institute of Public Health, Cuernavaca, Morelos, Mexico

    Isabelle Romieu, Matiana Ramírez-Aguilar & Irma Carmen del Lara-Sánchez

  4. Hospital Infantil de México Federico Gómez, Mexico City, Mexico

    Juan-Jose Sienra-Monge & Blanca Estela del Río-Navarro

  5. Department of Health Studies, The University of Chicago, Chicago, IL, USA

    Emily O. Kistner

  6. Norwegian Institute of Public Health, Oslo, Norway

    Håkon K. Gjessing

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  1. Huiling Li
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  2. Isabelle Romieu
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  3. Hao Wu
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  9. Håkon K. Gjessing
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  10. Stephanie J. London
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Correspondence to Stephanie J. London.

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Li, H., Romieu, I., Wu, H. et al. Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy. Hum Genet 121, 529–538 (2007). https://doi.org/10.1007/s00439-007-0337-z

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