Genotyping for NOD2 genetic variants and crohn disease: a metaanalysis.
BACKGROUND
Arg702Trp, Gly908Arg, and Leu1007fsinsC variants of the NOD2 gene (nucleotide-binding oligomerization domain containing 2; alias, CARD15) influence the risk of Crohn disease.


METHODS
We conducted a systematic review to examine whether Arg702Trp, Gly908Arg, and Leu1007fsinsC are equally important risk factors for Crohn disease. In addition, we used studies for which combined information from all genotypes was available to compare risks in simple heterozygotes, compound heterozygotes, and homozygotes. PubMed, EMBASE, and Web of Science were searched. Seventy-five articles (18 727 cases and 17 102 controls) met the inclusion criteria and contributed data to the metaanalyses.


RESULTS
The odds ratios per allele for Crohn disease were 2.2 (95% CI, 2.0-2.5) for Arg702Trp, 2.6 (2.2-2.9) for Gly908Arg, and 3.8 (3.4-4.3) for Leu1007fsinsC (z-test results: Arg702Trp vs Gly908Arg, P = 0.03; Arg702Trp vs Leu1007fsinsC, P < 0.001; Gly908Arg vs Leu1007fsinsC, P < 0.001). When all 3 genotypes were combined, odds ratios for Crohn disease were 2.4 (95% CI, 2.0-2.8) for simple heterozygotes, 9.0 (6.0-13.5) for compound heterozygotes, and 6.7 (4.1-10.9) for homozygotes, compared with noncarriers (z-test results: simple heterozygotes vs compound heterozygotes, P < 0.001; simple heterozygotes vs homozygotes, P < 0.001; compound heterozygotes vs homozygotes, P = 0.18).


CONCLUSIONS
The per-allele risk of Crohn disease was markedly higher for Leu1007fsinsC than for Arg702Trp and Gly908Arg. Combining all genotypes revealed the risks of Crohn disease for compound heterozygotes and homozygotes to be similar and markedly higher than for simple heterozygotes.
Yazdanyar
Shiva
S
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen DK-2730, Denmark.
Weischer
Maren
M
Nordestgaard
Børge G
BG
D000483:Alleles; D003424:Crohn Disease / Q000175:diagnosis* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein