TLR2, TLR4 and TLR9 polymorphisms and Crohn's disease in a New Zealand Caucasian cohort.
OBJECTIVE
Toll-like receptors (TLRs) have been identified as susceptibility genes for Crohn's disease (CD) in some, but not all, studies. Here we examined the association between candidate disease-susceptibility polymorphisms in the TLR2, TLR4 and TLR9 genes and CD in a New Zealand Caucasian population.


METHODS
The frequency of gene polymorphisms was examined in 182 CD patients and in 188 ethnically matched controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.


RESULTS
We could not detect any significant difference in the allele frequencies of polymorphisms in the TLR2 (R753Q, 0.029 vs 0.016, P = 0.25), TLR4 (D299G and T399I, 0.085 vs 0.071, P = 0.49; and 0.085 vs 0.082, P = 0.90), and TLR9 (-1237T/C, 0.154 vs 0.148, P = 0.82) genes between controls and patients, respectively. There was no evidence that the variant TLR alleles were associated with disease phenotype. However, combination of the datasets of published studies with our dataset confirmed that the TLR4 polymorphism 299G (P = 0.0005; OR of 1.42 [95% CI 1.17-1.74]) and the TLR9 polymorphism -1237C (P = 0.0416; OR of 1.33 [95% CI 1.01-1.75]) are associated with CD.


CONCLUSIONS
There was no evidence that the above variants of the TLR2, TLR4 and TLR9 genes are major risk factors for CD or influence disease phenotype in our New Zealand case-control study. Nevertheless, the significance of the TLR4 299G and TLR9-1237C associations with CD worldwide was confirmed by a meta-analysis test using our datasets and datasets from previously published studies.
Hong
Jiwon
J
Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Leung
Euphemia
E
Fraser
Alan G
AG
Merriman
Tony R
TR
Vishnu
Prakash
P
Krissansen
Geoffrey W
GW
D054458:Amplified Fragment Length Polymorphism Analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009520:New Zealand; D016017:Odds Ratio; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D044465:White People / Q000235:genetics*
C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9