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 23 November 2017

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News

Genes influence susceptibility and severity of Crohn's

The IBD5 locus influences susceptibility, progression, and need for surgery in Crohn's disease, and organic cation transporter genes 1/2 variants are not independent of the IBD5 haplotype, reports the latest issue of Gastroenterology.

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Polymorphisms in the organic cation transporter genes 1 and 2 represent disease-causing mutations within the IBD5 locus (chromosome 5q31).

Dr Colin Noble and colleagues investigated associations with disease susceptibility, phenotype, and evidence for epistasis with CARD15.

The research team assessed a total of 679 patients, of which 374 had Crohn's disease, 305 had ulcerative colitis and 294 were health controls.

Genotyping for single nucleotide polymorphisms IGR2096, IGR2198, and IGR2230, organic cation transporter genes 1 and 2 variants was performed using the TaqMan system.

The team found that the IBD5 organic cation transporter genes 1 and 2 polymorphisms were in strong linkage disequilibrium.

The IGR2198 variant allele frequency was associated with Crohn's disease
Gastroenterology

The IGR2198 variant allele frequency and homozygosity were associated with Crohn's disease compared with healthy controls.

Variant allelic frequency of organic cation transporter genes 1 and 2 polymorphism was associated with Crohn's.

The team also observed that homozygosity for the organic cation transporter genes 1- and 2-variants haplotype were associated with Crohn's.

The team noted that IGR2198 homozygosity and organic cation transporter genes 1/2 variatns homozygosity were associated with stricturing/penetrating disease on follow-up.

Using univariate analysis, the team found that disease progression was associated with IGR2198 and organic cation transporter genes variants homozygosity.

The IGR2198 and organic cation transporter genes homozygosity were associated with the need for surgery on multivariate analysis.

In the absence of the IBD5 risk haplotype, no association of organic cation transporter genes 1/2 variants with Crohn's disease was detected.

No associations were seen with ulcerative colitis.

Dr Noble and team conclude, “The IBD5 locus influences susceptibility, progression, and need for surgery in Crohn's disease.”

“The contribution of organic cation transporter genes 1/2 variants is not independent of the IBD5 haplotype.”

“A causative role for these genes remains plausible but is not yet proven.”

“Further genetic, functional, and expression data are now required.”

Gastroenterol 2005: 129(6): 1854-64
05 January 2006

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