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PMID: 21798578 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

IFNG genotype and sex interact to influence the risk of childhood asthma.

The Journal of allergy and clinical immunology ·Vol. 128 ·No. 3 ·2011-09-00 ·Pages 524-31

Loisel DA, Tan Z, Tisler CJ, Evans MD, Gangnon RE, Jackson DJ, Gern JE, Lemanske RF, Ober C

Abstract

Asthma is a complex disease characterized by sex-specific differences in incidence, prevalence, and severity, but little is known about the molecular basis of these sex-based differences. To investigate the genetic architecture of sex differences in asthma risk, we evaluated (1) associations between polymorphisms in the IFNG gene and childhood-onset asthma in combined and sex-specific samples and (2) interactions between polymorphisms and sex on asthma risk. Main and sex-interaction effects of IFNG genetic diversity on asthma risk and IFN-γ levels were examined in a birth cohort of children at high risk for asthma and allergic diseases. Replication of the genetic association was assessed in an independent sample of asthma cases. Significant genotype-sex interactions on asthma were observed for 2 IFNG single nucleotide polymorphisms, rs2069727 and rs2430561, which were in strong linkage disequilibrium with each other. In contrast, none of the 10 IFNG single nucleotide polymorphisms showed significant main effects on asthma. The observed genotype-sex interaction on asthma was characterized by nonadditivity; that is, heterozygous boys had the highest risk for asthma, and heterozygous girls had the lowest risk. The interaction effect was robust to other asthma risk factors but was limited to children who experienced wheezing illnesses with viral infections during the first 3 years of life. Genotype-sex interactions were also observed in the IFN-γ response to LPS in the first year of life. Finally, the sex-interaction effect was replicated in an independent population of childhood asthma cases. These results provide insight into the genetic basis of sex differences in asthma and highlight the potential importance of interactions among sex, genotype, and environmental factors in asthma pathogenesis.

MeSH Terms
Asthma/epidemiology,genetics Child Female Genetic Predisposition to Disease Genotype Humans Interferon-gamma/genetics,metabolism Male Polymorphism, Single Nucleotide Sex Factors
Chemicals
Interferon-gamma
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Loisel Dagan A
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. dloisel@bsd.uchicago.edu
Tan Zheng
Tisler Christopher J
Evans Michael D
Gangnon Ronald E
Jackson Daniel J
Gern James E
Lemanske Robert F
Ober Carole
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Article Info
Journal
The Journal of allergy and clinical immunology
Abbr.
J Allergy Clin Immunol
ISSN
1097-6825
DOI
10.1016/j.jaci.2011.06.016
Email
dloisel@bsd.uchicago.edu
Published
2011-09-00
Epub
2011-00-27
Pages
524-31
Language
English
Region
United States
NLM ID
1275002
PMCID
PMC3548570
Subset
IM
Grants
NHLBI NIH HHS · F32 HL095268-02 · United States
NHLBI NIH HHS · R01 HL085197-04 · United States
NHLBI NIH HHS · P01 HL070831 · United States
NCRR NIH HHS · M01 RR03186 · United States
NCRR NIH HHS · M01 RR00055 · United States
NHLBI NIH HHS · T32 HL007605 · United States
NCRR NIH HHS · M01 RR003186 · United States
NHLBI NIH HHS · F32 HL095268 · United States
NHLBI NIH HHS · R01 HL085197 · United States
NHLBI NIH HHS · P01 HL70831 · United States
NHLBI NIH HHS · P01 HL070831-05 · United States
NHLBI NIH HHS · T32 HL007605-28 · United States
NCRR NIH HHS · UL1 RR025011 · United States
NCRR NIH HHS · M01 RR000055 · United States
NIMH NIH HHS · R01 MH061879 · United States
NHLBI NIH HHS · R01 HL061879-04 · United States
NICHD NIH HHS · R01 HD061879 · United States
NHLBI NIH HHS · R01 HL61879 · United States
NCRR NIH HHS · UL1 RR025011-05 · United States
External Links
PubMed source DOI: 10.1016/j.jaci.2011.06.016 PMC Full Text View journal details
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