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Contribution of higher risk genes in Crohn's disease

This month's issue of the Inflammatory Bowel Diseases investigates the contribution of higher risk genes and European admixture to Crohn's disease in African Americans.

News image

African Americans are an admixed population of West African and European ancestry.

Crohn's disease susceptibility genes have not been established.

Dr Ming-Hsi Wang and colleagues evaluated the contribution of European admixture and major established risk genes to African Americans Crohn's disease.

The team identified 97 admixture informative markers genotyped for ancestry estimates using STRUCTURE.

The researchers reported that overall, 354 African Americans Crohn's disease cases, and 354 ethnicity-matched controls were genotyped for total 21 single nucleotide polymorphisms (SNPs) in ATG16L1, NOD2, IBD5, IL23R and IRGM by TaqMan or direct sequencing.

Association was evaluated by logistic regression, adjusted for ancestry.

The researchers found that European ancestry was similar among the Crohn's disease cases and controls.

Crohn's disease was associated with NOD2 carrier
Inflammatory Bowel Diseases

No significant admixture differences were observed among 211 to 227 cases stratified by phenotypic subclassifications including onset, surgery, site, and behavior.

The doctors noted that Crohn's disease was associated with NOD2 carrier, ATG16L1 Thr300Ala, SLC22A4 and SLC22A5 functional SNPs, and g-207c, and IL23R rs2201841, but not IRGM variants, nor 3 African ancestral NOD2 nonsynonymous variants.

IBD5 risk was recessive.

An all-minor allele IBD5 haplotype from European ancestry  was associated, whereas a more common haplotype isolating g-207c was not.

Dr Wang's team concludes that "Specific functional gene variations contribute significantly to African Americans Crohn's disease risk."

"Established NOD2, SLC22A4-A5, and ATG16L1 variants show increased Crohn's disease risk, with IBD5 recessive."

"Although Crohn's disease is more common in whites, European admixture is similar among African Americans cases and controls."

Inflamm Bowel Dis 2012: 18(12): 2277-2287
19 December 2012

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