Twins and family contribution to genetics of celiac disease

Celiac disease has a multifactorial background, but there is no doubt that the genetic component contributes most to the disease. The incidence within families is ten times the incidence among unrelated individuals. Concordance between monozygotic twins is more than 80%, as compared to the relatively low concordance (<20%) among dizygotic twins. Dizygotic twins have a concordance rate similar to siblings reared at different times. These data suggest that the genetic component is so strong that unshared environmental factors play a minor role in the pathogenesis of the disease. Monozygotic and dizygotic twins share the same environment in infancy, but their concordance rate is very different: the common environment likely explains a minor part of the variance in the incidence of the disease. First-degree relatives of celiac patients have a disease incidence of 10%, but this familial risk is not shared equally among all families. The risk is strongly related to the profile of HLA class II genes transmitted within the family. A double dose of the DQB1*02 gene is associated with a higher risk than a single dose of the same gene. The HLA profile of the proband allows a gross estimation of the risk of a new sibling, but the typing of parents gives a more accurate estimate of the risk of a newborn to develop celiac disease. Among families with a case, 40% will have a negligible risk of having an affected newborn, 30% will have a risk ranging from 1 to 10%, and 30% will have a risk of >20%. Copyright © 2008 S. Karger AG, Basel.