Nucleotide-binding oligomerization domain containing 1 (NOD1) haplotypes and single nucleotide polymorphisms modify susceptibility to inflammatory bowel diseases in a New Zealand caucasian population: a case-control study

doi:10.1186/1756-0500-2-52

BMC Research Notes
Volume 2

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Huebner C
Ferguson LR
Han DY
Philpott M
Barclay ML
Gearry RB
McCulloch A
Demmers PS
Browning BL

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Huebner C
Ferguson LR
Han DY
Philpott M
Barclay ML
Gearry RB
McCulloch A
Demmers PS
Browning BL
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Short Report

Nucleotide-binding oligomerization domain containing 1 (NOD1) haplotypes and single nucleotide polymorphisms modify susceptibility to inflammatory bowel diseases in a New Zealand caucasian population: a case-control study

Claudia Huebner¹^,7 , Lynnette R Ferguson¹^,7 , Dug Yeo Han¹^,7 , Martin Philpott¹^,7 , Murray L Barclay²^,3 , Richard B Gearry²^,3 , Alan McCulloch⁴^,7 , Pieter S Demmers⁵^,7 and Brian L Browning⁶

¹Discipline of Nutrition, The University of Auckland, Private Bag 92019, Auckland 1023, New Zealand

²Department of Gastroenterology, Christchurch Hospital, Christchurch 8011, New Zealand

³Department of Medicine, University of Otago, Christchurch, New Zealand

⁴Information Services, Plant and Food Research, Mosgiel 9053, New Zealand

⁵Information Services, AgResearch Limited, Mosgiel 9053, New Zealand

⁶Department of Statistics, The University of Auckland, Private Bag 92019, Auckland 1023, New Zealand

⁷Nutrigenomics, Web, New Zealand

author email corresponding author email

BMC Research Notes 2009, 2:52doi:10.1186/1756-0500-2-52


Published:	27 March 2009

Abstract

Background

The nucleotide-binding oligomerization domain containing 1 (NOD1) gene encodes a pattern recognition receptor that senses pathogens, leading to downstream responses characteristic of innate immunity. We investigated the role of NOD1 single nucleotide polymorphisms (SNPs) on IBD risk in a New Zealand Caucasian population, and studied Nod1 expression in response to bacterial invasion in the Caco2 cell line.

Findings

DNA samples from 388 Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis patients and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in NOD1, using the MassARRAY^®iPLEX Gold assay. Transcriptional activation of the protein produced by NOD1 (Nod1) was studied after infection of Caco2 cells with Escherichia coli LF82. Carrying the rs2075818 G allele decreased the risk of CD (OR = 0.66, 95% CI = 0.50–0.88, p < 0.002) but not UC. There was an increased frequency of the three SNP (rs2075818, rs2075822, rs2907748) haplotype, CTG (p = 0.004) and a decreased frequency of the GTG haplotype (p = 0.02).in CD. The rs2075822 CT or TT genotypes were at an increased frequency (genotype p value = 0.02), while the rs2907748 AA or AG genotypes showed decreased frequencies in UC (p = 0.04), but not in CD. Functional assays showed that Nod1 is produced 6 hours after bacterial invasion of the Caco2 cell line.

Conclusion

The NOD1 gene is important in signalling invasion of colonic cells by pathogenic bacteria, indicative of its' key role in innate immunity. Carrying specific SNPs in this gene significantly modifies the risk of CD and/or UC in a New Zealand Caucasian population.