Genetic contribution of the HLA region to the familial clustering of coeliac disease

Abstract

In order to assess the effect of the HLA region on familiality of coeliac disease (CD), we carried out a study on 121 CD index cases and 325 first degree relatives. The transmission disequilibrium test confirmed the importance of the HLA-DR3 haplotype in CD susceptibility. However, the different distortion found in affected children inheriting maternal or paternal DR3 alleles suggested that the sex of the parent might influence the risk conferred by this haplotype. The increase in risk to siblings of affected individuals relative to the risk in the general population (λ s ) and the contribution of the HLA genes to this clustering (λ sHLA ) have also been estimated. Non-overlapping data from the literature have been collected and combined with our sample to extend such analysis. Then, the percentage contribution of the HLA region to the development of CD among siblings was 36n2%. This result confirms that the HLA genotypes are an important genetic background to CD development but shows that additional susceptibility factors remain to be identified.

Promoter polymorphisms of the CD14 gene in Italian patients with coeliac disease

“…1 2 Undetected or untreated CD may cause other, more severe, complications later, such as autoimmune diseases, osteoporosis, neurological disorders, and infertility. 3 4 Several studies have shown CD clusters in families with a sibling relative risk of 20-60 and high concordance between monozygotic twins (75%), [5][6][7][8] which indicates a strong genetic component to coeliac disease. As expected in complex autoimmune diseases, human leukocyte antigen (HLA) linked genes are the main genetic factor involved in CD.…”

Candidate gene regions and genetic heterogeneity in gluten sensitivity

“…Furthermore, only a small fraction of DQ2 positive individuals ever develop coeliac disease although they eat gluten. The HLA locus was recently estimated to account for about 30% of familial clustering of coeliac disease in Italy 6. Other genetic components, as yet not identified, are likely to be involved.…”

Analysis of candidate genes on chromosome 19 in coeliac disease: an association study of the KIR and LILR gene clusters

“…A strong heritability is shown by the difference in concordance rates for coeliac disease between monozygotic and dizygotic twins (70–86% vs. 11–20%) (Polanko et al ., 1981; Greco et al ., 2002). It has been estimated that HLA linked genes contribute only about 40% of this heritability (Petronzelli et al ., 1997; Bevan et al ., 1999). There have been three published genome‐wide linkage studies (Table 1) (Zhong et al ., 1996; Greco et al ., 1998; King et al ., 2000).…”