Functional variants of OCTN cation transporter genes are associated with Crohn disease

Nature Genetics

Volumn 36, Issue 5, 2004, Pages 471-475

  Peltekova, Vanya D ^a,b   Wintle, Richard F ^c   Rubin, Laurence A ^a,c,d   Amos, Christopher I ^e   Huang, Qiqing ^e   Gu, Xiangjun ^e   Newman, Bill ^a,b   Van Oene, Mark ^c   Cescon, David ^a,b   Greenberg, Gordon ^a   Griffiths, Anne M ^f   St George Hyslop, Peter H ^a,c,g,h   Siminovitch, Katherine A ^a,b,c  

^a UNIVERSITY OF TORONTO   (Canada)

^b MOUNT SINAI HOSPITAL   (Canada)

^c Ellipsis Biotherapeutics Corporation   (Canada)

^d ST MICHAEL'S HOSPITAL   (Canada)

^e UNIVERSITY OF TEXAS   (United States)

^f HOSPITAL FOR SICK CHILDREN   (Canada)

^g UNIVERSITY OF TORONTO   (Canada)

^h UNIVERSITY HEALTH NETWORK   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

GENE PRODUCT; ORGANIC CATION TRANSPORTER GENE; PROTEIN SLC22A4; PROTEIN SLC22A5; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CROHN DISEASE; GENE CLUSTER; GENE INTERACTION; GENE LOCUS; GENE SEQUENCE; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; HAPLOTYPE; MISSENSE MUTATION; NONHUMAN; NUCLEOTIDE SEQUENCE; PREVALENCE; PRIORITY JOURNAL; PROMOTER REGION; SEQUENCE ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSCRIPTION INITIATION;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CARNITINE; CARRIER PROTEINS; CHROMOSOMES, HUMAN, PAIR 5; COHORT STUDIES; CROHN DISEASE; ELECTROPHORETIC MOBILITY SHIFT ASSAY; GENOTYPE; HAPLOTYPES; HELA CELLS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LINKAGE DISEQUILIBRIUM; MEMBRANE PROTEINS; MEMBRANE TRANSPORT PROTEINS; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; NOD2 SIGNALING ADAPTOR PROTEIN; ORGANIC ANION TRANSPORTERS; ORGANIC CATION TRANSPORT PROTEINS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS (GENETICS); RNA PROBES; SEQUENCE HOMOLOGY, AMINO ACID; VARIATION (GENETICS);

ANIMALIA;

EID: 2442585704     PISSN: 10614036     EISSN: None     Source Type: Journal    
DOI: 10.1038/ng1339     Document Type: Article

References (27)

1. Rioux, J.D. et al. Genome wide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am. J. Hum. Genet. 66, 1863-1870 (2000).
2. Ma, Y. et al. A genome-wide search identifies potential new susceptibility loci for Crohn's disease. Inflamm. Bowel Dis. 5, 271-278 (1999).
3. Rioux, J.D. et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat. Genet. 29, 223-228 (2001).
4. Burckhardt, G. & Wolff, N.A. Structure of renal organic anion and cation transporters. Am. J. Physiol. Renal Physiol. 278, F853-F866 (2000).
5. Ramensky, V., Bork, P. & Sunyaev, S. Human non-synonymous SNPs: server and survey. Nucleic Acids Res. 30, 3894-3900 (2002).
6. Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E.L.L. Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes. J. Mol. Biol. 305, 567-580 (2001).
7. Ng, P.C., Henikoff, J.G & Henikoff, S. PHAT: a transmembrane-specific substitution matrix. Predicted hydrophobic and transmembrane. Bioinformatics. 16, 760-766 (2000).
8. Newman, B. et al. CARD15 and HLA DRB1 alleles influence susceptibility and disease localization in Crohn's disease. Am. J. Gastroenterol. 99, 306-314 (2004).
9. Mirza, M.M. et al. Genetic evidence for interaction of the 5q31 cytokine locus and the CARD15 gene in Crohn Disease. Am. J. Hum. Genet. 72, 1018-1022 (2003).
10. Giallourakis, C. et al. IBD5 is a general risk factor for inflammatory bowel disease: replication of association with Crohn disease and identification of a novel association with ulcerative colitis. Am. J. Hum. Genet. 73, 205-211 (2003).
11. Lamhonwah, A.M., Skaug, J., Scherer, S.W. & Tein, I. A third human carnitine/organic cation transporter (OCTN3) as a candidate for the 5q31 Crohn's disease locus (IBD5). Biochem. Biophys. Res. Commun. 301, 98-101 (2003).
12. Wu, X., et al. Structural and functional characteristics and tissue distribution patterns of rat OCTN1, an organic cation transporter, cloned from placenta. Biochem. Biophys. Acta 1466, 315-327 (2000).
13. Wu, X. et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J. Pharmacol. Exp. Ther. 290, 1482-1492 (1999).
14. Elimrani, I. et al. Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 284, G863-G871 (2003).
15. Seth, P., Wu, X., Huang, W., Liebach, F.H. & Ganapathy, V. Mutation in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function. J. Biol. Chem. 274, 33388-33392 (1999).
16. Durán, J.M., Peral, M.J., Calonge, M.L & Ilundáin, A.A. Functional characterization of intestinal L-carnitine transport. J. Membr. Biol. 185, 65-74 (2002).
17. Tamai, I. et al. Cloning and characterization of a novel human pH-dependent organic cation transporter OCTN1. FEBS Lett. 419, 107-111 (1997).
18. Wu, C. Heat shock transcription factors: structure and regulation. Annu. Rev. Cell Dev. Biol. 11, 441-469 (1995).
19. Jurivich, D.A., Sistonen, L., Sarge, K.D., & Morimoto, R.I. Arachidonate is a potent modulator of human heat shock gene transcription. Proc. Natl. Acad. Sci. USA. 91, 2280-2284 (1994).
20. Tokuhiro, S. et al. An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat. Genet. 35, 341-348 (2003).
21. Ramsay, R.R. The carnitine acyltransferases: modulators of acyl-CoA-dependent reactions. Biochem. Soc. Trans. 28, 182-186 (2000).
22. Roediger, W.E & Nance, S. Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. Br. J. Exp. Pathol. 67, 773-782 (1986).
23. Wilson, P.W.F., Schaefer, E.J., Larson, M.G. & Ordovas, J.M. Apolipoprotein E alleles and risk of coronary artery disease. A meta-analysis. Arterioscler. Thromb. Vasc. Biol. 16, 1250-1255 (1996).
24. Saunders, A.M. et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43, 1467-1472 (1993).
25. Newman, B., Rubin, L.A. & Siminovitch, K.A. NOD2/CARD15 gene mutation is not associated with susceptibility to Wegener's Granulomatosis. J. Rheum. 30, 305-307 (2003).
26. Conlon, R.A & Rossant, J. Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox-2 genes in vivo. Development 116, 357-368 (1992).
27. Baler, R., Dahl, G. & Voellmy, R. Activation of human heat shock genes is accompanied by oligomerization, modification and rapid translocation of heat shock transcription factor HSF1. Mol. Cell. Biol. 13, 2486-2496 (1993).