Epidemiology and genetics in ulcerative colitis with special reference to twins and smoking

Abstract: In an epidemiologic study of ulcerative proctocolitis during the period 1963-1987, annual incidence rates increased fourfold and was during the last 10 years 13.1/105 inhabitants. The prevalence on December 31, 1987 was 234/105 inhabitants. Both rates are high but close to recent reports. No second peak in older age groups and no cohot t at higher risk for the disease was found. The male:female ratio was 1,59:1, and the highest incidence rate was seen in 20-40 year old men, who to a higher extent than women were ex-smokers. The distribution of affected male and female cases has changed during the last 60 years. A review of 56studies from 1930-1990 revealed that the earlier female predominance now has been replaced by a male predominance. The age at diagnosis increased 7 years by the end of the study period. With respect to the sex-distribution and the age at diagnosis, a hypothesis is proposed that an environmental factor, viz smoking, has caused this changing pattern. The genetic influence was analysed in a study of 36 twin pairs with ulcerative colitis, of which 16 pairs were monozygotic. The proband concordance rate among monozygotic twins was 6.3%, and the heritability of liability 0.53. No concordant pair was found among the dizygotic twins. A comparison indicated that the genetic influence was less significant inulcerative colitis than in Crohn's disease. Earlier reported twin pairs with ulcerative colitis probably overestimated concordance rates due to selection bias. Abnormal colonic glycoproteins have earlier been reported in ulcerative colitis. Colonic glycoproteins were analysed in the monozygotic twins according to the method described by Podolsky et al. Similar alterations in glycoprotein composition were found in both the twins with ulcerative colitis and in their healthy twin siblings, indicating that changes in colonicglycoproteins probably are genetically defined, precede the onset of colitis and are not a secondary consequence of inflammation. A case-control study of smoking habits at the time of diagnosis was performed among 260 cases and 455 matched population controls to evaluate the association between smoking and ulcerative colitis. Compared to lifetime non-smokers, a reduced risk of acquiring ulcerative colitis was seen among smokers (relative risk 0.6) which seemed to be dose dependant. Exsmokers had an increased risk, which was especially increased in former heavy smokers (relative risk 4.4). A study of primary sclerosing cholangitis in ulcerative colitis showed a prevalence of 3.7%. Male excess and extensive to total colitis was found in the cases complicated with cholangitis, which in most cases was asymptomatic and had a non-progressive course. As 15 of the 16 monozygotic twin pairs were discordant for ulcerative colitis, the combination of identical genotype, shared environment in childhood and adolescence, similar levels of colonic glycoproteins and similar smoking habits is apparently not sufficient to cause manifest colitis and additional factors are needed.