POLYMORPHISM OF THE IL-1 GENE-COMPLEX IN EPSTEIN-BARR-VIRUS SERONEGATIVE AND SEROPOSITIVE ADULT-BLOOD DONORS

Epstein-Barr virus (EBV) seronegativity is rare in adults. To examine whether genetic differences would explain this, we studied the genetic polymorphisms of the genes of the interleukin-l (IL-1) complex in ser onegative adults. These cytokines (i.e. IL-1 alpha, IL-1 beta and IL-1 receptor antagonist, IL-1RA) regulate, in several ways, the inflammat ory reactions of the body. In each of these genes there are polymorphi c sites and the various alleles differ in their frequency in several d iseases of inflammatory nature. In 400 healthy blood donors (from 18 t o 60 years of age) there were 20 (5%) seronegative persons. The freque ncy of allele 2 of the IL-1 beta gene (base exchange polymorphism at p osition -511 from the transcriptional start site) was decreased in the seronegative patients (0.20 versus 0.42 in the seropositive patients, P < 0.05, chi(2)-test). Moreover, the frequency of allele 2 of the TL -IRA (polymorphism defined by variable numbers of 86-bp repeats in int ron 2) was slightly, but not significantly, decreased in the seronegat ive patients. Alleles of these two loci are known to be associated, bu t in the seronegative patients this association was abnormal: Il out o f 20 (55%) were of the IL-1RA-2 negative/IL-1 beta-2 negative type, wh ile of the seropositive patients, 25% were of this type (P < 0.01, chi (2)-test). These data suggest that immunological differences, dependin g on cytokine gene polymorphisms, regulate the resistance to EBV infec tion.