ABSTRACT
INTRODUCTION: Environmental factors may play an important role in the pathogenesis of IBD. The history of patients of the German IBD twin study was analyzed by questionnaires and interviews. METHODS: Randomly selected German monozygotic (MZ) and dizygotic (DZ) twins with at least one sibling suffering from IBD (n=512) were characterized in detail including demography, medical history and concomitant medications. Controls comprised of non-twin IBD patients (n=392) and healthy subjects (n=207). RESULTS: The most significant variables that were associated with Crohn's disease (CD) or ulcerative colitis (UC) included living abroad before time of diagnosis (OR, 4.32; 95% CI, 1.57-13.69), high frequency of antibiotic use (MZ CD OR, 5.03; 95% CI 1.61-17.74, DZ CD OR, 7.66; 95% CI, 3.63-16.82, MZ UC OR, 3.82; 95% CI, 1.45-10.56, DZ UC OR, 3.08; CI, 1.63-5.92), high consumption of processed meat including sausage (MZ CD OR, 7.9; 95% CI, 2.15-38.12, DZ CD OR, 10.75; 95% CI, 4.82-25.55, MZ UC OR, 5.69; 95% CI, 1.89-19.48, DZ UC OR, 18.11; 95% CI, 7.34-50.85), and recall of bacterial gastrointestinal infections (MZ CD OR, 15.9; 95% CI, 4.33-77.14, DZ CD OR, 17.21; 95% CI, 4.47-112.5, MZ UC OR, 5.87; 95% CI, 1.61-28.0, DZ UC OR, 11.34; 95% CI, 4.81-29.67). CONCLUSIONS: This study reinforced the association of life style events, in particular a specific dietary and infections history, with IBD. Alteration of gut flora or alterations of the mucosal immune system in reactivity to the flora could be an important factor to explain the relationship between life-style and disease.
Subject(s)
Colitis, Ulcerative/etiology , Crohn Disease/etiology , Diseases in Twins/etiology , Adolescent , Adult , Aged , Child , Communicable Diseases/complications , Comorbidity , Diet , Female , Germany , Humans , Life Style , Male , Middle Aged , Risk Factors , Surveys and Questionnaires , Twins, Dizygotic , Twins, Monozygotic , Young AdultABSTRACT
BACKGROUND: Genetic predisposition as a cause of inflammatory bowel disease (IBD) has been proven by both family and twin studies and genetic variants associated with the disease have been identified. The aim of our study was to determine the concordance rates for IBD in German twin pairs and to evaluate clinical characteristics of concordant and discordant twin pairs. METHODS: Patients with IBD were asked to participate and complete a questionnaire that contained questions about zygosity, demographic data, and medical history. RESULTS: A total of 189 twin pairs in which at least 1 member had IBD were recruited (68 monozygotic and 121 dizygotic pairs). Within monozygotic pairs, 11 out of 31 (35%) were concordant for Crohn's disease (CD) and 6 out of 37 (16%) for ulcerative colitis (UC). Two of the 58 (3%) dizygotic pairs with CD and 1 out of 63 (2%) dizygotic pairs with UC were concordant for the disease. In 14 out of 20 (70%) discordant monozygotic CD pairs and 25 out of 31 (81%) discordant monozygotic pairs with UC, the first-born was affected by IBD. For discordant dizygotic twins, the first in birth order had IBD in 33 out of 56 (59%) pairs with CD and 40 out of 62 (64.5%) pairs with UC. CONCLUSIONS: This study confirms a stronger genetic influence in CD than in UC. The high preponderance in being affected of the first-born twin and the fact that concordance was only 35% for CD and 16% for UC monozygotic twins highlight the important role of environmental trigger factors.
Subject(s)
Colitis, Ulcerative/genetics , Crohn Disease/genetics , Adult , Cohort Studies , Diseases in Twins , Female , Germany/epidemiology , Humans , Male , Middle Aged , Surveys and Questionnaires , Twins, Dizygotic , Twins, MonozygoticABSTRACT
Previous longevity studies of related individuals such as twins or siblings based on the major gene model have shown that the frequency and the relative risk of mortality of a beneficial allele in the population could be estimated. If, in addition to survival data for related individuals, the genetic markers data are available, one could try to locate the longevity allele in the genome. In the case where the phenotypic trait is life span or age at onset of disease, a two-step procedure can be used. First, the parameters of bivariate survival functions must be estimated from bivariate survival data for twins without markers. The second step is focused on determining the position of longevity genes between respective markers. To calculate the joint distribution of inheritance vector and genetic markers, the hidden Markov chain technique is used. This approach is illustrated with a simulation example for one longevity gene.