Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma.
BACKGROUND
Allergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (TSLP) in the pathogenesis of AR has not been studied.


OBJECTIVE
To test for associations between variants in TSLP, TSLP-related genes, and AR in children with asthma.


METHODS
We genotyped 15 single nucleotide polymorphisms (SNPs) in TSLP, OX40L, IL7R, and RXRα in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for TSLP, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.


RESULTS
Across the three cohorts, the T allele of TSLP SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10-4). Our findings were significant after accounting for multiple comparisons. SNPs in OX40L, IL7R, and RXRα were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.


CONCLUSIONS
TSLP SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for TSLP in the pathogenesis of AR in children with asthma.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. supinda@post.harvard.edu.
Supinda
S
Bunyavanich
Erik
E
Melen
Jemma B
JB
Wilk
Mark
M
Granada
Manuel E
ME
Soto-Quiros
Lydiana
L
Avila
Jessica
J
Lasky-Su
Gary M
GM
Hunninghake
Magnus
M
Wickman
Göran
G
Pershagen
George T
GT
O'Connor
Scott T
ST
Weiss
Juan C
JC
Celedón
Clin Exp Allergy. 2009 Jun;39(6):798-806
19400908
Chin Med J (Engl). 2009 Oct 5;122(19):2303-7
20079130
J Immunol. 2001 Jul 1;167(1):336-43
11418668
N Engl J Med. 2010 Sep 23;363(13):1211-1221
20860503
J Exp Med. 2007 Feb 19;204(2):253-8
17242164
J Exp Med. 2005 Nov 7;202(9):1213-23
16275760
Allergy. 2010 Feb;65(2):256-63
19796208
Am J Hum Genet. 2007 Sep;81(3):559-75
17701901
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14795-800
16199515
Int J Immunogenet. 2007 Jun;34(3):149-51
17504502
Nat Immunol. 2002 Jul;3(7):673-80
12055625
JAMA. 2007 Aug 22;298(8):880-93
17712072
J Exp Med. 2000 Sep 4;192(5):659-70
10974032
J Allergy Clin Immunol. 2009 Sep;124(3 Suppl):S43-70
19592081
J Allergy Clin Immunol. 2004 Dec;114(6):1282-7
15577824
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W621-5
16845085
Environ Health Perspect. 2008 Aug;116(8):1077-84
18709160
J Allergy Clin Immunol. 2007 Jul;120(1):84-90
17561245
Allergy. 2008 Apr;63 Suppl 86:8-160
18331513
Nat Rev Genet. 2006 May;7(5):385-94
16619052
Am J Hum Genet. 2004 Feb;74(2):367-9
14740322
J Allergy Clin Immunol. 2009 Aug;124(2):222-9
19539984
Am J Hum Genet. 2009 May;84(5):581-93
19426955
Am J Respir Crit Care Med. 2008 Apr 15;177(8):830-6
18244952
J Allergy Clin Immunol. 2006 Dec;118(6):1375-81
17157669
Eur J Immunol. 2008 Jun;38(6):1487-92
18461563
J Manag Care Pharm. 2004 Jul-Aug;10(4):310-7
15298529
Nat Genet. 2010 Apr;42(4):289-91
20208534
Cell Tissue Res. 2009 Nov;338(2):283-93
19763625
Am J Respir Cell Mol Biol. 2009 Mar;40(3):368-74
18787178
Am J Respir Crit Care Med. 2004 Nov 15;170(10):1057-65
15282200
Adv Immunol. 2009;101:1-25
19231591
J Clin Invest. 2007 Dec;117(12):3868-78
18060034
Acta Otolaryngol. 2009 Mar;129(3):297-301
18720075
J Allergy Clin Immunol. 2002 Mar;109(3):514-6
11898000
Hum Mol Genet. 2007 Feb 1;16(3):243-53
17142250
Nat Immunol. 2000 Jul;1(1):59-64
10881176
Pediatrics. 2005 Jan;115(1):129-34
15629992
Thorax. 2007 Sep;62(9):758-66
17504817
Allergy. 2010 Dec;65(12):1566-75
20560908
J Allergy Clin Immunol. 2004 Mar;113(3):415-9
15007339
Allergy. 2008 Jan;63(1):47-57
17822448
Bioinformatics. 2005 Jan 15;21(2):263-5
15297300
J Immunol. 2008 Aug 15;181(4):2790-8
18684970
Nucleic Acids Res. 2007 Jan;35(Database issue):D26-31
17148475
Cytokine. 2008 Jun;42(3):325-9
18440239
Am J Respir Crit Care Med. 2007 Nov 1;176(9):849-57
17702965
J Immunol. 2005 Jun 15;174(12):8183-90
15944327
Nature. 2003 Dec 18;426(6968):789-96
14685227
Allergy. 2005 Mar;60(3):338-42
15679719
Control Clin Trials. 1999 Feb;20(1):91-120
10027502