TY - JOUR
T1 - Genotyping for NOD2 genetic variants and crohn disease: a metaanalysis
AU - Yazdanyar, Shiva
AU - Weischer, Maren
AU - Nordestgaard, Børge
N1 - Keywords: Alleles; Crohn Disease; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Nod2 Signaling Adaptor Protein
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1373/clinchem.2009.127126
DO - 10.1373/clinchem.2009.127126
M3 - Journal article
C2 - 19713276
SN - 0009-9147
VL - 55
SP - 1950
EP - 1957
JO - Clinical Chemistry
JF - Clinical Chemistry
IS - 11
ER -