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Polymorphisms in the tumor necrosis factor/lipopolysaccharides pathway in Crohn disease in the Jewish Ashkenazi population.

Abstract：

OBJECTIVE:Tumor necrosis factor (TNF)-alpha plays a role in the inflammatory process in Crohn disease, a disease with an apparent polygenic basis. We investigated whether polymorphisms in multiple genes involved in the lipopolysaccharide-TNF inflammatory pathway are independently associated with Crohn disease in the Jewish Ashkenazi population. Polymorphisms in CD14, Toll-like receptor 4 (TLR4), and TNF-alpha were studied. In addition, we investigated polymorphisms in the TNF-alpha converting enzyme (TACE) gene, which to date has not been studied for an association with Crohn disease. PATIENTS AND METHODS:To examine whether TLR4 Asp299Gly, CD14-260C/T, TNF-1031T/C, TNF-863C/A, TNF-857C/T, TACE-172C/T, and TACE-154C/A polymorphisms are associated with Crohn disease in the Ashkenazi Jewish population, we analyzed families with at least 1 child with Crohn disease for association with these mutations using a family-based association test (transmission disequilibrium test) for analysis. RESULTS:The allelic frequency in the patient population of TLR4 G allele was 8.0%, CD14 T allele was 51.3%, TNF-1031C was 18.8%, TNF-863A was 14.2%, TNF-857T was 25.2%, TACE172T was 20.7%, and TACE154A was 24.5%. The transmission disequilibrium test transmitted:untransmitted (T:U) result for TLR4G was T:U = 32:20, for CD14T was T:U = 103:88, for TNF-1031C was T:U = 48:56, for TNF-863A was T:U = 39:42, for TNF-857T was T:U = 63:62, for TACE-172C/T was T:U = 48:59, and for TACE-154C/A was T:U = 52:55. No statistically significant associations were observed. CONCLUSIONS:The transmission disequilibrium test did not demonstrate preferential transmission of these variants in Jewish Ashkenazi patients with Crohn disease. These results suggest that these polymorphisms in the TNF/lipopolysaccharide pathway play little or no role in susceptibility to Crohn disease in the Jewish Ashkenazi population.

journal_name

J Pediatr Gastroenterol Nutr

journal_title

Journal of pediatric gastroenterology and nutrition

authors

Silbermintz A,Levine J,Weinstein T,Silver J

doi

10.1097/MPG.0b013e3181653ab5

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

546-50

issue

eissn

0277-2116

issn

1536-4801

pii

00005176-200805000-00011

journal_volume

pub_type

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Polymorphisms in the tumor necrosis factor/lipopolysaccharides pathway in Crohn disease in the Jewish Ashkenazi population.