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Functional variants of OCTN cation transporter genes are associated with Crohn disease.
- Source :
-
Nature genetics [Nat Genet] 2004 May; Vol. 36 (5), pp. 471-5. Date of Electronic Publication: 2004 Apr 11. - Publication Year :
- 2004
-
Abstract
- Crohn disease is a chronic, inflammatory disease of the gastrointestinal tract. A locus of approximately 250 kb at 5q31 (IBD5) was previously associated with susceptibility to Crohn disease, as indicated by increased prevalence of a risk haplotype of 11 single-nucleotide polymorphisms among individuals with Crohn disease, but the pathogenic lesion in the region has not yet been identified. We report here that two variants in the organic cation transporter cluster at 5q31 (a missense substitution in SLC22A4 and a G-->C transversion in the SLC22A5 promoter) form a haplotype associated with susceptibility to Crohn disease. These variants alter transcription and transporter functions of the organic cation transporters and interact with variants in another gene associated with Crohn disease, CARD15, to increase risk of Crohn disease. These results suggest that SLC22A4, SLC22A5 and CARD15 act in a common pathogenic pathway to cause Crohn disease.
- Subjects :
- Amino Acid Sequence
Amino Acid Substitution
Carnitine metabolism
Cohort Studies
Electrophoretic Mobility Shift Assay
Genotype
Haplotypes
HeLa Cells
Humans
Linkage Disequilibrium
Molecular Sequence Data
Nod2 Signaling Adaptor Protein
Organic Anion Transporters
Polymorphism, Single Nucleotide
Promoter Regions, Genetic genetics
RNA Probes
Sequence Homology, Amino Acid
Solute Carrier Family 22 Member 5
Symporters
Carrier Proteins genetics
Chromosomes, Human, Pair 5 genetics
Crohn Disease genetics
Genetic Variation
Intracellular Signaling Peptides and Proteins
Membrane Proteins genetics
Membrane Transport Proteins
Mutation, Missense
Organic Cation Transport Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 1061-4036
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 15107849
- Full Text :
- https://doi.org/10.1038/ng1339