NOD1/CARD4, a member of the pattern-recognition receptor family, is a perfect candidate as a susceptibility gene for Crohn's disease. Since only limited and conflicting data are available on G796A polymorphisms in inflammatory bowel disease patients, we set out to study the effect of this polymorphism on the susceptibility and course of Crohn's disease in the Hungarian population.Four hundred thirty-four unrelated Crohn's disease patients (age at presentation: 28.6+/-9.6 years, female/male: 210/224, duration of Crohn's disease: 8.2+/-6.9 years) and 200 healthy subjects (blood donors) and 136 non-inflammatory bowel disease gastrointestinal controls with chronic gastritis were investigated. NOD1 G796A was detected by using polymerase chain reaction/restriction fragment length polymorphism. Detailed clinical phenotypes were determined by reviewing the medical charts.The frequencies of the variant alleles of NOD1 G796A differed significantly between the Crohn's disease patients and both healthy (GG 49.5% vs. 67%; AG 41.5% vs. 28%; and AA 9.0% vs. 5.2%; p<0.0001) and non-inflammatory bowel disease controls with chronic gastritis. Carriage of the single nucleotide polymorphism of NOD1 G796A proved to be a highly significant risk factor for Crohn's disease compared to both healthy (p<0.0001, OR: 2.1, 95% CI: 1.5-2.9) and non-inflammatory bowel disease controls with chronic gastritis (p=0.008). Significant associations were not found between the different genotypes and the demographic data on the patients or the clinical characteristics of Crohn's disease. The different polymorphisms of pattern-recognition receptors (e.g. NOD2/CARD15 SNP8, SNP12 and SNP13 mutations, the TLR4 D299G polymorphism and NOD1 G796A) did not reveal a mutual basis.Our results suggest that carriage of the NOD1 G796A mutation increases susceptibility for Crohn's disease in the Hungarian population.