A second-generation association study of the 5q31 cytokine gene cluster and the interleukin-4 receptor in asthma.

Abstract:

:We have analyzed a dense set of single-nucleotide polymorphisms (SNPs) and microsatellites spanning the T-helper cytokine gene cluster (interleukins 3, 4, 5, 9, and 13, interferon regulatory factor-1, colony-stimulating factor-2, and T-cell transcription factor-7) on 5q31 and the gene encoding the interleukin-4 receptor (IL4R) on 16p12 among Finnish families with asthma. As shown by haplotype pattern mining analysis, the number of disease-associated haplotype patterns differed from that expected for the 129Q allele polymorphism in IL13 for high serum total immunoglobulin (Ig) E levels, but not for asthma. The same SNP also yielded the best haplotype associations. For IL4R, asthma-associated haplotype patterns, most spanning the S411L polymorphism, showed suggestive association. However, these haplotypes consisted of the major alleles for the intracellular part of the receptor and were very common among both patients and controls. The minor alleles 503P and 576R have been reported to be associated with decreased serum IgE levels and changes in the biological activity of the protein, especially when inherited together. In the Finnish population, these two polymorphisms segregated in strong linkage disequilibrium. Our data support previous findings regarding L4R, indicating that 503P and 576R may act as minor protecting alleles for IgE-mediated disorders.

journal_name

Genomics

journal_title

Genomics

authors

Kauppi P,Lindblad-Toh K,Sevon P,Toivonen HT,Rioux JD,Villapakkam A,Laitinen LA,Hudson TJ,Kere J,Laitinen T

doi

10.1006/geno.2001.6613

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

35-42

issue

1-2

eissn

0888-7543

issn

1089-8646

pii

S0888-7543(01)96613-3

journal_volume

77

pub_type

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