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NOD2 Variants and Crohn’s Disease

June 5, 2001
Abstraction Template
     
Key variables & Description Article

Reference
Complete the bibliographic reference for the article according to AJE format.

 

 Ogura Y, Bonen DK, Inohara N, et al.  A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease.  Nature 2001;411:603-606

Category of HuGE information
Specify the types of information (from the list below) available in the article:

  1. Prevalence of gene variant
  2. Gene-disease association
  3. Gene-environment interaction
  4. Gene-gene interaction
  5. Genetic test evaluation/monitoring

 

1. Prevalence of gene variant
2. Gene-disease association

 

 

Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study

 

 Hypothesis:  Mutations in the NOD2 gene are associated with Crohn’s disease.

Gene(s)
Identification of the following:

  1. Gene name
  2. Chromosome location
  3. Gene product/function
  4. Alleles
  5. OMIM #

 
  1. Gene: NOD2
  2. Chromosome location: 16q12
  3. Gene product/function:  protein involved in cell signaling pathways that have a role in innate immune response  
  4. Alleles: 1-BP ins 3020
  5. OMIM #: 605956, also 266600 (IBD1)

Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral)

 

N/A

Health outcome(s)
Identification of the major health outcome(s) studied

 

1. Crohn’s disease
2. ulcerative colitis
Study design
Specification of the type of study design(s)
  1. Case-control
  2. Cohort 
  3. Cross-sectional
  4. Descriptive or case series
  5. Clinical trial
  6. Population screening

 

 1. Case-control
Case definition
For study designs 1, 4, and 5, define the following if available:
  1. Disease case definition
  2. Exclusion criteria
  3. Gender
  4. Race/ethnicity
  5. Age
  6. Time period
  7. Geographic location
  8. Number of participants

 
  1. Disease case definition: clinical diagnosis of Crohn’s disease
  2. Exclusion criteria: only one case per family
  3. Gender: not specified
  4. Race/ethnicity: Caucasian (included Ashkenazi Jewish)
  5. Age: not specified
  6. Time period: not specified
  7. Geographic location: Univ of Chicago, Johns Hopkins Univ, Univ of Pittsburgh
  8. Number of participants: 416
Control definition
For study design 1, define the following if available:
  1. Control selection criteria
  2. Matching variables
  3. Exclusion criteria
  4. Gender
  5. Race/ethnicity
  6. Age
  7. Time period
  8. Geographic location
  9. Number of participants

 
  1. Control selection criteria:  not specified 
  2. Matching variables: not specified
  3. Exclusion criteria:  not specified
  4. Gender: not specified
  5. Race/ethnicity: Caucasian
  6. Age: not specified
  7. Time period: not specified
  8. Geographic location: Chicago, Baltimore, San Francisco, Germany
  9. Number of participants: 287

Cohort definition
For study designs 2, 3, and 6, define the following if available:

  1. Cohort selection criteria
  2. Exclusion criteria
  3. Gender
  4. Race/ethnicity
  5. Age
  6. Time period
  7. Geographic location
  8. Number of participants

 

 N/A
Assessment of environment factors
For studies that include gene-environment interactions, define the following, if available:
  1. Environmental factor
  2. Exposure assessment
  3. Exposure definition
  4. Number of participants with exposure data (% of total eligible)

 

N/A
Genotyping
Specify the following:
  1. Gene
  2. DNA source
  3. Methodology
  4. Number of participants genotyped (% of total eligible) 

 
  1. Gene: NOD2
  2. DNA source:  not specified 
  3. Methodology: multiplex PCR, confirmed by sequencing
  4. Participants genotyped:  416 cases, 287 controls
Results
Describe the major results under each of the following HuGE categories. Include tables when data are provided:
  1. Prevalence of gene variant
  2. Gene-disease association
  3. Gene-environment interaction
  4. Gene-gene interaction
  5. Genetic test evaluation/monitoring

 

1.  Prevalence of gene variant

1-BP INS, 3020C allele denoted “ins” in tables; “+” denotes wt 

Genotype

Cases
#    %

Controls
 #         %

+/+

ins/+

ins/ins

359    (86.3)

46   (11.1)

11    (2.6)

264    (92.0)

23    (8.0)

0    (0.0)

2. Gene-disease association

Genotype
OR (95% CI)
+/+ 

ins/+

ins/ins
Ref

  1.5

 17.6

 

Conclusion
State the author's overall conclusions from the study

 

The 3020insC variant of NOD2 is associated with Crohn’s disease, suggesting an etiologic link to the innate immune response to bacterial components.
Comments
Provide additional insight, including methodologic issues and/or concerns about the study

This report demonstrates the association between the 3020insC variant of NOD2 and Crohn’s disease in a family study using the transmission disequilibrium test, as well as in the case-control study, for which only one member of each family was selected as a case.  Little information is provided about the selection of cases/families and controls.  Alleles were assumed to be in Hardy-Weinberg equilibrium among controls to estimate an expected value for the zero cell (0.46), which was used to arrive at an OR of 17.6 for homozygosity.  The 3020insC variant was not associated with ulcerative colitis (allele frequency 3.0%). 

AF for homozygosity was 2.5%, and for heterozygosity 3.7%; therefore, this alone variant is not responsible for most cases of Crohn’s disease.  However, the finding is important because it points to a possible etiologic pathway in a serious disease that until now has been idiopathic.

 
Last Updated August 25, 2004