ETIOLOGY OF CROHNS-DISEASE - CURRENT DATA

Both genetic and environmental factors appear to play an aetiologic ro le in Crohn's disease. The hypothesis of genetic sus ceptibility is ba sed on the frequency of familial forms (6-33%) and higher relative ris k in first degree relatives (x10 to x21), Three genetic segregation an alyses have defined a genetic model favouring autosomal recessive tran smission and incomplete penetration. The frequency of the deleterious allele would be 0.01 in the general population. One third of all patie nts would be homozygous. To date, no genetic marker has been found for Crohn's disease although in one study, molecular biology techniques r evealed a significant association between the HLA-DR1, DQW5 genotypes, and the association DR1/DQW5, and Crohn's disease. There are also man y arguments in favour of an environmental cause, including: increased incidence since the Second World War, a north-south incidence gradient (established in the US and probable in Europe), predominance in urban areas. In addition, 21 conjugal forms were recently reported in the U S, including 14 which appeared after marriage. We have also observed 1 0 conugal forms in a limited area in northern France and in Belgium. S moking has also been shown to have a detrimental effect, perhaps via m odifications in the microcirulation of the intestinal wall. Despite co ntradictory results, oestrogen-progesterone treatment does not appear to increase the risk of Crohn's disease and there is no convincing evi dence that any particular food could be incriminated. In contradiction with a widely believed myth, there is no evidence showing that psychi atric factors have an effect on appearance or aggravation of the disea se. Perinatal infection has however been recently shown to affect inci dence and subjects born during periods of flu epidemics have a higher relative risk Still other studies have emphasized the dual role of gen etic/environmental factors. Based on current knowledge, the sequence l eading to the appearance of Crohn's disease would include one or more perinatal event(s) such as viral infection acting on a genetically sus ceptible subject and leading to modified immune response in a vulnerab le system (perinatal period). Later in life an aggression (environment ) would lead to inappropriate immune response. Current research is dir ected towards identifying infectious agents capable of triggering the disease and on markers of genetic susceptibility.