Analysis of single-nucleotide polymorphisms in the interleukin-4 receptor gene for association with inflammatory bowel disease

Citation
Mg. Olavesen et al., Analysis of single-nucleotide polymorphisms in the interleukin-4 receptor gene for association with inflammatory bowel disease, IMMUNOGENET, 51(1), 2000, pp. 1-7
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
IMMUNOGENETICS
ISSN journal
0093-7711 → ACNP
Volume
51
Issue
1
Year of publication
2000
Pages
1 - 7
Database
ISI
SICI code
0093-7711(200001)51:1<1:AOSPIT>2.0.ZU;2-Z
Abstract
Genetic linkage analysis in families with multiple cases of inflammatory bo wel disease (IBD) has mapped a gene which confers susceptibility to IBD to the pericentromeric region of chromosome 16 (IBD1). The Linked region inclu des the interleukin(IL)-4 receptor gene (IL4R). Since IL-4 regulation and e xpression are abnormal in IBD, the IL4R gene is thus both a positional and functional candidate for IBD1. We screened the gene for single-nucleotide p olymorphisms (SNPs) by fluorescent chemical cleavage analysis, and tested a subset of known and novel SNPs for allelic association with IBD in 355 fam ilies, which included 435 cases of Crohn's disease and 329 cases of ulcerat ive colitis. No association was observed between a haplotype of four SNPs ( val50ile, gln576arg, A3044G, G3289A) and either the Crohn's disease or ulce rative colitis phenotypes using the transmission disequilibrium test. There was also no evidence for association when the four markers were analyzed i ndividually. The results indicate that these variants are not significant g enetic determinants of IBD, and that the IL4R gene is unlikely to be IBD1. Linkage disequilibrium analyses showed that the val50ile and gln576arg vari ants are in complete equilibrium with each other, although they are separat ed by only about 21 kilobases of genomic DNA. This suggests that a very den se SNP map may be required to exclude or detect disease associations with s ome candidate genes.