Asthma and lower airway diseaseIFNG genotype and sex interact to influence the risk of childhood asthma
Section snippets
Ethics statement
Written informed consent was obtained from all participants. The Childhood Origins of Asthma (COAST) study was approved by the University of Wisconsin Human Subjects Committee and the University of Chicago Institutional Review Board. The Chicago Asthma Genetics study was approved by the University of Chicago Institutional Review Board.
COAST study subjects
A total of 289 subjects were enrolled at birth into the COAST study between November 1998 and May 2000, as previously described.26 Each newborn was required to
Results
Ten SNPs at the IFNG locus were genotyped in 234 COAST children of European descent (Fig 1, A). Observed genotype counts at all 10 SNPs did not differ from those expected under Hardy-Weinburg equilibrium (P > .05, data not shown). Pairwise LD, measured by means of the r2 statistic, was observed among a subset of IFNG SNPs (Fig 1, B). By using an r2 cutoff of 0.75, the 10 IFNG SNPs fell into 5 LD bins: 5 SNPs comprised bin 1 (rs2069705, rs1861493, rs2069718, rs2193050, and rs2193048), 2 SNPs
Discussion
Identification of the genetic and environmental factors that contribute to the developmental and sex-specific patterns of asthma prevalence is complicated by potential interactions between them.38, 39 Here we provide evidence that interactions between sex and IFNG polymorphisms contribute to the risk of childhood asthma. Heterozygosity at 2 IFNG SNPs (rs2069727 and rs2430561) was protective in girls but associated with increased asthma risk in boys. This genotype-sex interaction was itself
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Cited by (34)
Asthma over the Adult Life Course: Gender and Hormonal Influences
2019, Clinics in Chest MedicineCorrelation study between ADA and IFN-γ gene polymorphisms and the risk of developing tuberculous pericarditis
2018, GeneCitation Excerpt :At present, there are few studies on the relationship between IFN-γ gene polymorphism and TBP risk. In this study, the rs2069707 locus of IFN-γ was studied, and SNPs at this locus may be the target for a drug (Loisel et al., 2011). Our results showed that the frequency of the G allele at the rs2069707 locus of IFN-γ in TBP patients was significantly higher than that in non TBP patients, indicating that the rs2069707 SNP of IFN-γ is also a risk factor for contracting TBP.
Gender and Gene Regulation in Human Immunity
2017, Principles of Gender-Specific Medicine: Gender in the Genomic Era: Third EditionSex-related differences in pulmonary physiologic outcome measures in a high-risk birth cohort
2015, Journal of Allergy and Clinical ImmunologyIndividuality and Variation of Personal Regulomes in Primary Human T Cells
2015, Cell SystemsCitation Excerpt :Multiple studies have documented gender-specific association of allelic variants at IFNG regulatory elements or IFNG protein levels with human disease. For example, IFNG variants are associated with multiple sclerosis (Kantarci et al., 2008) and asthma (Loisel et al., 2011) in males, but not females, but the mechanisms are not known. NeST (also known as IFNG-AS1 or TMEVPG1) is located proximal to IFNG and encodes an lncRNA that is required to program active chromatin state and promote expression of IFNG (Gomez et al., 2013).
Genomic architecture of asthma differs by sex
2015, GenomicsCitation Excerpt :The presence of SNP-by-sex and probe-by-sex interaction is supported by previous studies. Genetic association studies of have implicated sex-specific effects in INFG [19], TSLP and asthma [26] and CTLA4 with allergic response [27]. Gene expression studies also implicate sex interactions in placental global gene expression in response to asthma [28], IL17BR in allergic response [29] and overall gene expression in humans [30], as well as for asthma-related genes in mice [6,7,31].
Supported by National Institutes of Health grants R01 HL61879, P01 HL70831, M01 RR03186, R01 HL085197, and M01 RR00055. D.A.L. was supported by National Institutes of Health grants F32 HL095268 and T32 HL007605.
Disclosure of potential conflict of interest: D. J. Jackson has received research support from Pharmaxis, the National Institutes of Health, and the American Academy of Allergy, Asthma & Immunology/GlaxoSmithKline. J. E. Gern is on the scientific advisory board of and holds stock options for 3V Biosciences; has consulted and holds stock options for EraGen Biosciences; has consulted for Synairgen, Boehringer Inhgelheim, Pulmatrix, GlaxoSmithKline, and Biota; and has received research support from AstraZeneca and Merck. R. F. Lemanske, Jr, is a speaker for Merck, Doembecher Children’s Hospital, Washington University, the Medicus Group, the Park Nicolet Institute, the ACAAI, the LA Allergy Society, the Michigan Allergy/Asthma Society, the Medical College of Wisconsin, the Fund for Medical Research and Education (Detroit), the Children’s Hospital of Minnesota, the Toronto Allergy Society, the AAAAI, Beaumont Hospital, the University of Illinois, the Canadian Society of Allergy and Clinical Immunology, New York Presbyterian, the Med Media Educational Group, Onpointe Medical Communication, the Medical University of South Carolina, Health Matters Communication, Bishop McCann, Donohue Purohit Miller, the Center for Health Care Education, the University of California San Francisco, the American Thoracic Society, the University of Iowa, Indiana University, the American Lung Association of the Upper Midwest, Vanderbilt University, and Rochester Children’s Hospital; is a consultant and speaker for AstraZeneca; is a consultant for Map Pharmaceuticals, Gray Consulting, Smith Research, the Merck Childhood Asthma Network, Novartis, Quintiles/Innovax, RC Horowitz & Co, International Meetings and Science, Scienomics, Scientific Therapeutics, Gray Consulting, and Cognimed Inc; is an author of Up-to-Date; and is a textbook Editor for Elsevier. C. Ober receives research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest.
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Dr Tan is currently affiliated with the Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY.