Faculty Collaboration Database

Contribution of OCTN variants within the IBD5 locus to pediatric onset Crohn's disease. Am J Gastroenterol 2006 Jun;101(6):1354-61

Date

06/15/2006

Pubmed ID

16771961

DOI

10.1111/j.1572-0241.2006.00564.x

Scopus ID

2-s2.0-33744808327 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

BACKGROUND & AIMS: The IBD5 locus on chromosome 5q31 is a confirmed Crohn's disease (CD) susceptibility locus in adults. Recently, two polymorphisms in the organic cation transporter (OCTN) gene cluster within the IBD5 locus have been found to be associated with CD. Although the original report of significant linkage to IBD5 was in families with at least one case of early age at onset CD, there are no published reports on the role of OCTN genes in pediatric onset CD. We performed a comprehensive analysis of OCTN variants in an independent, exclusively pediatric onset CD cohort and examined the genotype/phenotype correlations.

METHODS: 264 Caucasian CD children (172 of them were trios) were genotyped along with 527 controls for OCTN1 (SLC22A4 C1672T), OCTN2 (SLC22A5 G-207C), and two haplotype-tagging SNPs (IGR2230 and IGR2198).

RESULTS: TDT confirmed the association of SLC22A4 and SLC22A5. Case-control analysis of the SLC22A4 1672T, SLC22A5-207C diplotype showed significant association (p=0.04) with CD susceptibility compared with controls. Little correlation was seen with regard to clinical phenotype and the SLC22A4/SLC22A5 diplotype. There was no significant interaction between the SLC22A4/SLC22A5 diplotype and the three CD-associated CARD15 SNPs.

CONCLUSIONS: We confirm the association of the OCTN variants (SLC22A4 and SLC22A5) in pediatric onset CD as seen in adult CD cohorts. However, when an extended IBD5 haplotype was examined, no independent association between OCTN variants and pediatric onset CD can be demonstrated. Compared with adults, a relatively weak association of the OCTN variants was observed in our CD cohort. No definitive genotype-phenotype correlation or gene-gene interactions with CARD15 were observed. Although the IBD5 locus is associated with pediatric onset CD, no definitive conclusions can be drawn about OCTN variants as causative genes in pediatric CD at this point.

Author List

Babusukumar U, Wang T, McGuire E, Broeckel U, Kugathasan S

Authors

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Child, Preschool
Chromosomes, Human, Pair 5
Crohn Disease
Female
Genetic Predisposition to Disease
Genetic Variation
Genotype
Haplotypes
Humans
Infant
Infant, Newborn
Male
Organic Cation Transport Proteins
Phenotype
Polymorphism, Genetic
Solute Carrier Family 22 Member 5
Symporters