Genetics of celiac disease.HLA and non-HLA genes

Resumen

Although the mode of inheritance of celiac disease is still unknown,it has been known for a long time that Genetics participates in thesusceptibility to the disease. Studies on the prevalence of CD inaffected families, and especially those comparing twin pairs, have beenvery useful to estimate the proportion in which environmental andgenetic factors contribute to the development of this complex disorder.According to these studies, Genetics is a fundamental player both inthe triggering and in the latter development of CD.In general, it is well accepted that the proportion of monozygotic oridentical twins concordant for CD is around 75-86%, while in the caseof dizygotic twins, this proportion is reduced to 16-20%. Thisdifference between mono- and dizygotic twins has allowed scientists toestimate the genetic component of CD, which is higher than what hasbeen calculated for other immunological complex diseases, such as type1 diabetes (T1D) (around 30% concordance in monozygotic and 6% indizygotic twins)1. Moreover, concordance rates between sib pairs anddizygotic twins are almost the same, indicating that the environmentalcomponent has a minimum contribution to the risk of developing CD.In summary, accumulated evidence suggests that CD has a very stronggenetic component and it has been calculated that the heritability ofthis disease (proportion of the risk of suffering from CD attributable togenetic factors, compared to environmental determinants) is around87%2. The largest portion of the genetic risk to develop CD comes fromthe presence of certain Human Leucocyte Antigen (HLA) alleles.However, even if the role of these HLA molecules is essential in thepathogenesis of the disease, their contribution to the heredity is modest, and thus, it has been hypothesized on the existence of manysmall effect, non-HLA susceptibility loci.