Identification of NOD2/CARD15 mutations in Malaysian patients with Crohn's disease

Kek Heng Chua, Ida Hilmi, Ching Ching Ng, Tzy Lui Eng, Shanthi Palaniappan, Way Seah Lee, Khean Lee Goh

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 patientsand 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. Conclusion: These findings suggest the presence of novel DPM in the NOD2/ CARD15 gene in Asian patients with CD.

Original languageEnglish
Pages (from-to)124-130
Number of pages7
JournalJournal of Digestive Diseases
Volume10
Issue number2
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Crohn Disease
Mutation
Ethnic Groups
Population
Genes
Jews
Age of Onset
Developed Countries
Restriction Fragment Length Polymorphisms
Demography
Polymerase Chain Reaction

Keywords

  • Malaysian
  • Mutation
  • NOD2/CARD15
  • Variant

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Chua, K. H., Hilmi, I., Ng, C. C., Eng, T. L., Palaniappan, S., Lee, W. S., & Goh, K. L. (2009). Identification of NOD2/CARD15 mutations in Malaysian patients with Crohn's disease. Journal of Digestive Diseases, 10(2), 124-130. https://doi.org/10.1111/j.1751-2980.2009.00374.x

Identification of NOD2/CARD15 mutations in Malaysian patients with Crohn's disease. / Chua, Kek Heng; Hilmi, Ida; Ng, Ching Ching; Eng, Tzy Lui; Palaniappan, Shanthi; Lee, Way Seah; Goh, Khean Lee.

In: Journal of Digestive Diseases, Vol. 10, No. 2, 2009, p. 124-130.

Research output: Contribution to journalArticle

Chua, KH, Hilmi, I, Ng, CC, Eng, TL, Palaniappan, S, Lee, WS & Goh, KL 2009, 'Identification of NOD2/CARD15 mutations in Malaysian patients with Crohn's disease', Journal of Digestive Diseases, vol. 10, no. 2, pp. 124-130. https://doi.org/10.1111/j.1751-2980.2009.00374.x
Chua, Kek Heng ; Hilmi, Ida ; Ng, Ching Ching ; Eng, Tzy Lui ; Palaniappan, Shanthi ; Lee, Way Seah ; Goh, Khean Lee. / Identification of NOD2/CARD15 mutations in Malaysian patients with Crohn's disease. In: Journal of Digestive Diseases. 2009 ; Vol. 10, No. 2. pp. 124-130.
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abstract = "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 patientsand 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. Conclusion: These findings suggest the presence of novel DPM in the NOD2/ CARD15 gene in Asian patients with CD.",
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AU - Hilmi, Ida

AU - Ng, Ching Ching

AU - Eng, Tzy Lui

AU - Palaniappan, Shanthi

AU - Lee, Way Seah

AU - Goh, Khean Lee

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AB - 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 patientsand 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. Conclusion: These findings suggest the presence of novel DPM in the NOD2/ CARD15 gene in Asian patients with CD.

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