Identification of NOD2/CARD15 mutations in Malaysian patients with Crohn's disease.
OBJECTIVE
The NOD2/CARD15 gene has been identified as an important susceptibility gene for Crohn's disease (CD) but the three common disease predisposing mutations (DPM) found in developed countries have not been identified in Asian populations. The aim of our study was to look for the DPM in our multiracial population and to discover whether there were any differences in the three major ethnic groups; Malay, Chinese and Indian.


METHODS
Blood samples from consecutive CD patients and healthy controls were obtained and analyzed for the three common mutations (R702W, G908R, 1007fs) but in addition to this, we also looked for the SNP5 and JW1 variants which are associated with CD in Ashkenazi Jews. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to identify the mutations, which was confirmed by sequencing. The baseline socio-demography and clinical characteristics of the CD patients were recorded.


RESULTS
Overall 45 patients (three Malays, 15 Chinese, 26 Indians and one other) with confirmed CD and 300 controls were recruited. The three common DPM were not observed in either the CD patients or the controls. Neither the SNP5 nor the JW1 mutation was found in any of the controls. However, the SNP5 mutation was identified in six (13.3%) Indian CD patients and the JW1 mutation in eight CD patients who are different from those carrying the SNP5 mutation: one Malay (33.3%), two Chinese (13.3%), one other (Portuguese) and four Indians (15.4%). The presence of SNP5 was strongly associated with CD in the Indian population and that of JW1 was strongly associated with CD overall and in each of the major ethnic groups. There was a trend towards a younger age of onset and stricturing disease in patients carrying the JW1 mutation.


CONCLUSIONS
These findings suggest the presence of novel DPM in the NOD2/CARD15 gene in Asian patients with CD.
Department of Molecular Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Kek Heng
KH
Chua
Ida
I
Hilmi
Ching Ching
CC
Ng
Tzy Lui
TL
Eng
Shanthi
S
Palaniappan
Way Seah
WS
Lee
Khean-Lee
KL
Goh
D000328:Adult; D000368:Aged; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein