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Allergy, Asthma & Clinical Immunology
Published in: Allergy, Asthma & Clinical Immunology 1/2010

Open Access 01-12-2010 | Research

Birth order modifies the effect of IL13 gene polymorphisms on serum IgE at age 10 and skin prick test at ages 4, 10 and 18: a prospective birth cohort study

Authors: Ikechukwu U Ogbuanu, Wilfried J Karmaus, Hongmei Zhang, Tara Sabo-Attwood, Susan Ewart, Graham Roberts, Syed H Arshad

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2010

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Abstract

Background

Susceptibility to atopy originates from effects of the environment on genes. Birth order has been identified as a risk factor for atopy and evidence for some candidate genes has been accumulated; however no study has yet assessed a birth order-gene interaction.

Objective

To investigate the interaction of IL13 polymorphisms with birth order on allergic sensitization at ages 4, 10 and 18 years.

Methods

Mother-infant dyads were recruited antenatally and followed prospectively to age 18 years. Questionnaire data (at birth, age 4, 10, 18); skin prick test (SPT) at ages 4, 10, 18; total serum IgE and specific inhalant screen at age 10; and genotyping for IL13 were collected. Three SNPs were selected from IL13: rs20541 (exon 4, nonsynonymous SNP), rs1800925 (promoter region) and rs2066960 (intron 1). Analysis included multivariable log-linear regression analyses using repeated measurements to estimate prevalence ratios (PRs).

Results

Of the 1456 participants, birth order information was available for 83.2% (1212/1456); SPT was performed on 67.4% at age 4, 71.2% at age 10 and 58.0% at age 18. The prevalence of atopy (sensitization to one or more food or aeroallergens) increased from 19.7% at age 4, to 26.7% at 10 and 41.1% at age 18. Repeated measurement analysis indicated interaction between rs20541 and birth order on SPT. The stratified analyses demonstrated that the effect of IL13 on SPT was restricted only to first-born children (p = 0.007; adjusted PR = 1.35; 95%CI = 1.09, 1.69). Similar findings were noted for firstborns regarding elevated total serum IgE at age 10 (p = 0.007; PR = 1.73; 1.16, 2.57) and specific inhalant screen (p = 0.034; PR = 1.48; 1.03, 2.13).

Conclusions

This is the first study to show an interaction between birth order and IL13 polymorphisms on allergic sensitization. Future functional genetic research need to determine whether or not birth order is related to altered expression and methylation of the IL13 gene.
Literature
1.
Vercelli D: Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol. 2008, 8: 169-182. 10.1038/nri2257.CrossRefPubMed
2.
Allam JP, Zivanovic O, Berg C, Gembruch U, Bieber T, Novak N: In search for predictive factors for atopy in human cord blood. Allergy. 2005, 60: 743-750. 10.1111/j.1398-9995.2005.00815.x.CrossRefPubMed
3.
4.
5.
Escoubet-Lozach L, Glass CK, Wasserman SI: The role of transcription factors in allergic inflammation. J Allergy Clin Immunol. 2002, 110: 553-564. 10.1067/mai.2002.128076.CrossRefPubMed
6.
Gluckman PD, Hanson MA, Cooper C, Thornburg KL: Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008, 359: 61-73. 10.1056/NEJMra0708473.PubMedCentralCrossRefPubMed
7.
Ege MJ, Bieli C, Frei R, van Strien RT, Riedler J, Ublagger E, Schram-Bijkerk D, Brunekreef B, van Hage M, Scheynius A, Pershagen G, Benz MR, Lauener R, von Mutius E, Braun-Fahrlander C: Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. J Allergy Clin Immunol. 2006, 117: 817-823. 10.1016/j.jaci.2005.12.1307.CrossRefPubMed
8.
Martinez FD: Toward asthma prevention--does all that really matters happen before we learn to read?. N Engl J Med. 2003, 349: 1473-1475. 10.1056/NEJMe030041.CrossRefPubMed
9.
Karmaus W, Botezan C: Does a higher number of siblings protect against the development of allergy and asthma? A review. J Epidemiol Community Health. 2002, 56: 209-217. 10.1136/jech.56.3.209.PubMedCentralCrossRefPubMed
10.
Bernsen RM, de Jongste JC, Wouden van der JC: Birth order and sibship size as independent risk factors for asthma, allergy, and eczema. Pediatr Allergy Immunol. 2003, 14: 464-469. 10.1046/j.0905-6157.2003.00108.x.CrossRefPubMed
11.
Cullinan P, MacNeill SJ, Harris JM, Moffat S, White C, Mills P, Newman Taylor AJ: Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study. Thorax. 2004, 59: 855-861. 10.1136/thx.2003.019877.PubMedCentralCrossRefPubMed
12.
Karmaus W, Arshad H, Mattes J: Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years. Am J Epidemiol. 2001, 154: 909-915. 10.1093/aje/154.10.909.CrossRefPubMed
13.
Dekker GA, Robillard PY, Hulsey TC: Immune maladaptation in the etiology of preeclampsia: a review of corroborative epidemiologic studies. Obstet Gynecol Surv. 1998, 53: 377-382. 10.1097/00006254-199806000-00023.CrossRefPubMed
14.
Goldberg S, Israeli E, Schwartz S, Shochat T, Izbicki G, Toker-Maimon O, Klement E, Picard E: Asthma prevalence, family size, and birth order. Chest. 2007, 131: 1747-1752. 10.1378/chest.06-2818.CrossRefPubMed
15.
Zekveld C, Bibakis I, Bibaki-Liakou V, Pedioti A, Dimitroulis I, Harris J, Newman Taylor AJ, Cullinan P: The effects of farming and birth order on asthma and allergies. Eur Respir J. 2006, 28: 82-88. 10.1183/09031936.06.00021305.CrossRefPubMed
16.
Heinzmann A, Jerkic SP, Ganter K, Kurz T, Blattmann S, Schuchmann L, Gerhold K, Berner R, Deichmann KA: Association study of the IL13 variant Arg110Gln in atopic diseases and juvenile idiopathic arthritis. J Allergy Clin Immunol. 2003, 112: 735-739. 10.1016/S0091-6749(03)01887-6.CrossRefPubMed
17.
Hunninghake GM, Soto-Quiros ME, Avila L, Su J, Murphy A, Demeo DL, Ly NP, Liang C, Sylvia JS, Klanderman BJ, Lange C, Raby BA, Silverman EK, Celedon JC: Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood. J Allergy Clin Immunol. 2007, 120: 84-90. 10.1016/j.jaci.2007.04.032.CrossRefPubMed
18.
Liu X, Beaty TH, Deindl P, Huang SK, Lau S, Sommerfeld C, Fallin MD, Kao WH, Wahn U, Nickel R: Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study. J Allergy Clin Immunol. 2003, 112: 382-388. 10.1067/mai.2003.1635.CrossRefPubMed
19.
Liu X, Beaty TH, Deindl P, Huang SK, Lau S, Sommerfeld C, Fallin MD, Kao WH, Wahn U, Nickel R: Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study. J Allergy Clin Immunol. 2004, 113: 489-495. 10.1016/j.jaci.2003.12.037.CrossRefPubMed
20.
Liu X, Nickel R, Beyer K, Wahn U, Ehrlich E, Freidhoff LR, Bjorksten B, Beaty TH, Huang SK: An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German multicenter atopy study (MAS-90). J Allergy Clin Immunol. 2000, 106: 167-170. 10.1067/mai.2000.107935.CrossRefPubMed
21.
Sadeghnejad A, Karmaus W, Hasan Arshad S, Ewart S: IL13 gene polymorphism association with cord serum immunoglobulin E. Pediatr Allergy Immunol. 2007
22.
Karmaus W, Arshad SH, Sadeghnejad A, Twiselton R: Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance. Clin Exp Allergy. 2004, 34: 853-859. 10.1111/j.1365-2222.2004.01959.x.CrossRefPubMed
23.
Kurukulaaratchy RJ, Fenn MH, Waterhouse LM, Matthews SM, Holgate ST, Arshad SH: Characterization of wheezing phenotypes in the first 10 years of life. Clin Exp Allergy. 2003, 33: 573-578. 10.1046/j.1365-2222.2003.01657.x.CrossRefPubMed
24.
Arshad SH, Hide DW: Effect of environmental factors on the development pf allergic disorders in infancy. Journal of Allergy and Clinical Immunology. 1992, 90: 235-241. 10.1016/0091-6749(92)90077-F.CrossRefPubMed
25.
Kurukulaaratchy RJ, Fenn M, Twiselton R, Matthews S, Arshad SH: The prevalence of asthma and wheezing illnesses amongst 10-year-old schoolchildren. Respir Med. 2002, 96: 163-169. 10.1053/rmed.2001.1236.CrossRefPubMed
26.
Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21: 263-265. 10.1093/bioinformatics/bth457.CrossRefPubMed
27.
Arshad SH, Karmaus W, Kurukulaaratchy R, Sadeghnejad A, Huebner M, Ewart S: Polymorphisms in the interleukin 13 and GATA binding protein 3 genes and the development of eczema during childhood. Br J Dermatol. 2008, 158: 1315-1322. 10.1111/j.1365-2133.2008.08565.x.PubMedCentralCrossRefPubMed
28.
Sadeghnejad A, Karmaus W, Arshad SH, Kurukulaaratchy R, Huebner M, Ewart S: IL13 gene polymorphisms modify the effect of exposure to tobacco smoke on persistent wheeze and asthma in childhood, a longitudinal study. Respir Res. 2008, 9: 2-10.1186/1465-9921-9-2.PubMedCentralCrossRefPubMed
29.
Sadeghnejad A, Meyers DA, Bottai M, Sterling DA, Bleecker ER, Ohar JA: IL13 promoter polymorphism 1112C/T modulates the adverse effect of tobacco smoking on lung function. Am J Respir Crit Care Med. 2007, 176: 748-752. 10.1164/rccm.200704-543OC.CrossRefPubMed
30.
Park HW, Lee JE, Kim SH, Kim YK, Min KU, Kim YY, Cho SH: Genetic variation of IL13 as a risk factor of reduced lung function in children and adolescents: A cross-sectional population-based study in Korea. Respir Med. 2008
31.
Bottema RW, Reijmerink NE, Kerkhof M, Koppelman GH, Stelma FF, Gerritsen J, Thijs C, Brunekreef B, van Schayck CP, Postma DS: Interleukin 13, CD14, pet and tobacco smoke influence atopy in three Dutch cohorts: the allergenic study. Eur Respir J. 2008, 32: 593-602. 10.1183/09031936.00162407.CrossRefPubMed
32.
Sadeghnejad A, Karmaus W, Davis S, Kurukulaaratchy RJ, Matthews S, Arshad SH: Raised cord serum immunoglobulin E increases the risk of allergic sensitisation at ages 4 and 10 and asthma at age 10. Thorax. 2004, 59: 936-942. 10.1136/thx.2004.024224.PubMedCentralCrossRefPubMed
33.
Arshad SH, Twiselton R, Smith J, Hide DW: Influence of genetic and environmental factors on the level of IgE at birth. Pediatric Allergy and Immunology. 1992, 3: 79-83. 10.1111/j.1399-3038.1992.tb00030.x.CrossRef
34.
Arshad SH, Stevens M, Hide DW: The effect of genetic and environmental factors on the prevalence of allergic disorders at the age of two years. Clinical and Experimental Allergy. 1993, 23: 504-511. 10.1111/j.1365-2222.1993.tb03238.x.CrossRefPubMed
35.
Hide DW, Arshad SH, Twiselton R, Stevens M: Cord serum IgE: an insensitive method for prediction of atopy. Clin Exp Allergy. 1991, 21: 739-743. 10.1111/j.1365-2222.1991.tb03204.x.CrossRefPubMed
36.
Ogbuanu IU, Karmaus W, Arshad SH, Kurukulaaratchy RJ, Ewart S: Effect of breastfeeding duration on lung function at age 10 years: a prospective birth cohort study. Thorax. 2009, 64: 62-66. 10.1136/thx.2008.101543.PubMedCentralCrossRefPubMed
37.
Howard TD, Whittaker PA, Zaiman AL, Koppelman GH, Xu J, Hanley MT, Meyers DA, Postma DS, Bleecker ER: Identification and association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population. Am J Respir Cell Mol Biol. 2001, 25: 377-384.CrossRefPubMed
38.
Kang MJ, Lee SY, Kim HB, Yu J, Kim BJ, Choi WA, Jang SO, Hong SJ: Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction. Pharmacogenet Genomics. 2008, 18: 551-558. 10.1097/FPC.0b013e3282fe94c5.CrossRefPubMed
39.
SNPper, The Children's Hospital Informatics Program (CHIP) Bioinformatics Tools. Harvard school of medicine (Boston, MA). 2005
40.
Graves PE, Kabesch M, Halonen M, Holberg CJ, Baldini M, Fritzsch C, Weiland SK, Erickson RP, von Mutius E, Martinez FD: A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J Allergy Clin Immunol. 2000, 105: 506-513. 10.1067/mai.2000.104940.CrossRefPubMed
41.
42.
Ober C, Hoffjan S: Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun. 2006, 7: 95-100. 10.1038/sj.gene.6364284.CrossRefPubMed
43.
Chuang JC, Jones PA: Epigenetics and microRNAs. Pediatr Res. 2007, 61: 24R-29R. 10.1203/pdr.0b013e3180457684.CrossRefPubMed
44.
45.
Bjornsson HT, Fallin MD, Feinberg AP: An integrated epigenetic and genetic approach to common human disease. Trends Genet. 2004, 20: 350-358. 10.1016/j.tig.2004.06.009.CrossRefPubMed
46.
Gosden RG, Feinberg AP: Genetics and epigenetics--nature's pen-and-pencil set. N Engl J Med. 2007, 356: 731-733. 10.1056/NEJMe068284.CrossRefPubMed
47.
Wegienka G, London SJ, Johnson CC, Ownby DR: Interpregnancy interval might affect the risk of childhood atopy. J Allergy Clin Immunol. 2004, 113: 169-171. 10.1016/j.jaci.2003.10.012.PubMedCentralCrossRefPubMed
48.
Pembrey M: Genetic epidemiology: some special contributions of birth cohorts. Paediatr Perinat Epidemiol. 2004, 18: 3-7. 10.1111/j.1365-3016.2004.00530.x.CrossRefPubMed
49.
Lin YC, Wen HJ, Lee YL, Guo YL: Are maternal psychosocial factors associated with cord immunoglobulin E in addition to family atopic history and mother immunoglobulin E?. Clin Exp Allergy. 2004, 34: 548-554. 10.1111/j.1365-2222.2004.1928.x.CrossRefPubMed
50.
Liu CA, Wang CL, Chuang H, Ou CY, Hsu TY, Yang KD: Prenatal prediction of infant atopy by maternal but not paternal total IgE levels. J Allergy Clin Immunol. 2003, 112: 899-904. 10.1016/j.jaci.2003.08.030.CrossRefPubMed
Metadata
Title
Birth order modifies the effect of IL13 gene polymorphisms on serum IgE at age 10 and skin prick test at ages 4, 10 and 18: a prospective birth cohort study
Authors
Ikechukwu U Ogbuanu
Wilfried J Karmaus
Hongmei Zhang
Tara Sabo-Attwood
Susan Ewart
Graham Roberts
Syed H Arshad
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Allergy, Asthma & Clinical Immunology / Issue 1/2010
Electronic ISSN: 1710-1492
DOI
https://doi.org/10.1186/1710-1492-6-6

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