Yazdanyar S, Nordestgaard BG (Herlev Hospital, Copenhagen University Hospital, University of Copenhagen; and Bispebjerg Hospital, Copenhagen University Hospital, University of Copenhagen; Herlev, Denmark). NOD2/CARD15 genotype, cardiovascular disease and cancer in 43 600 individuals from the general population. J Intern Med 2010; 268: 162-170. Objectives. The NOD2/CARD15 gene is involved in the innate immune response, and thus in inflammation. Three polymorphisms in this gene (Arg702Trp rs2066844, Gly908Arg rs2066845 and Leu1007fsinsC rs5743293) have been associated with increased risk of the inflammatory bowel disease, the Crohn's disease. We tested whether these polymorphisms are also associated with increased risk of cardiovascular disease and cancer, in which the innate immune system and inflammation may influence pathogenesis. Design, setting and subjects. We genotyped 43 596 white individuals from two large Danish general population cohorts followed for 31 years: the Copenhagen City Heart Study (n = 10 597) and the Copenhagen General Population Study (n = 32 999). We examined the risk of cardiovascular disease (2743 and 3890, respectively, in the two studies) and cancer (2144 and 3241, respectively) by NOD2/CARD15 genotype using Cox and logistic regressions in both studies. To maximize statistical power, the three NOD2/CARD15 genetic variants were analysed together as follows: noncarriers for all three variants, heterozygotes for one of the three variants and homozygotes for one of the three variants pooled with compound heterozygotes for two variants. Results. Multifactorially adjusted hazard ratios for cardiovascular disease and cancer in NOD2/CARD15 heterozygotes or homozygotes/compound heterozygotes versus noncarries did not differ from 1.0 in the Copenhagen City Heart Study or in the Copenhagen General Population Study. The corresponding multifactorially adjusted odds ratios likewise did not differ from 1.0 in either study. Conclusions. The NOD2/CARD15 Arg702Trp, Gly908Arg and Leu1007fsinsC polymorphisms were not associated with increased risk of cardiovascular disease or cancer in the Danish general population