title: Gene polymorphisms, breast-feeding, and development of food sensitization in early childhood.
abstract: BACKGROUND
  The effect of breast-feeding on the development of allergic disease is uncertain. There are no data that show whether this relationship varies by individual genotypes.
  
  
  OBJECTIVE
  We sought to evaluate the effect of breast-feeding and gene-breast-feeding interactions on food sensitization (FS) in a prospective US birth cohort.
  
  
  METHODS
  This study included 970 children who were prospectively followed since birth. Breast-feeding history was obtained from a standardized questionnaire interview. FS was defined as a specific IgE level of 0.35 kU(A)/L or greater to any of 8 common food allergens. Eighty-eight potentially functional single nucleotide polymorphisms (SNPs) were genotyped from 18 genes involved in innate immunity or T(H)1/T(H)2 balance. Logistic regression models were used to test the effects of breast-feeding and gene-breast-feeding interactions on FS, with adjustment for pertinent covariates.
  
  
  RESULTS
  Children who were ever breast-fed (n = 739), including exclusively breast-fed children, were at a 1.5 (95% CI, 1.1-2.1; P = .019) times higher risk of FS than never breast-fed children (n = 231). This association was significantly modified by rs425648 in the IL-12 receptor β1 gene (IL12RB1; P for interaction = .0007): breast-feeding increased the risk of FS (odds ratio, 2.0; 95% CI, 1.4-3.1; P = .0005) in children carrying the GG genotype but decreased the risk (odds ratio, 0.6; 95% CI, 0.3-1.4; P = .252) in children carrying the GT/TT genotype. Similar interactions were observed for SNPs in the Toll-like receptor 9 (TLR9; rs352140) and thymic stromal lymphopoietin (TSLP; rs3806933) genes. The interaction between the combined genotypes of the 3 SNPs and breast-feeding on FS was even stronger (P for interaction < 10⁻⁵).
  
  
  CONCLUSIONS
  Our data suggest that the effect of breast-feeding on FS was modified by SNPs in the IL12RB1, TLR9, and TSLP genes both individually and jointly. Our findings underscore the importance of considering individual genetic variations in assessing this relationship.
authors.affiliation: Mary Ann and J. Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL 60614, USA. xhong@childrensmemorial.org
authors.forename: Xiumei
authors.initials: X
authors.lastname: Hong
authors.forename: Guoying
authors.initials: G
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Lester
authors.initials: L
authors.lastname: Arguelles
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.forename: Colleen
authors.initials: C
authors.lastname: Pearson
authors.forename: Kathryn
authors.initials: K
authors.lastname: Ortiz
authors.forename: Anthony
authors.initials: A
authors.lastname: Bonzagni
authors.forename: Stephanie
authors.initials: S
authors.lastname: Apollon
authors.forename: Lingling
authors.initials: L
authors.lastname: Fu
authors.forename: Deanna
authors.initials: D
authors.lastname: Caruso
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Pongracic
authors.forename: Robert
authors.initials: R
authors.lastname: Schleimer
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
authors.forename: Howard
authors.initials: H
authors.lastname: Bauchner
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D001942:Breast Feeding / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005512:Food Hypersensitivity / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D055815:Young Adult
chemical_list: C498762:CRLF2 protein, human; C508438:IL12RB1 protein, human; D018121:Receptors, Cytokine; D053707:Receptors, Interleukin-12; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9