Uncovering Family Affairs in Autoimmune Endocrine Diseases


Christopher Torrilla, Syed Sufyan Hussain, Frank Waldron-Lynch, Anne Dornhorst



Type 1 Diabetes mellitus (T1DM) is an autoimmune disease characterised by pancreatic β-cell destruction and absolute insulin deficiency. Histological and immuno-genetic evidence suggests T1DM is a T-cell mediated autoimmune process. Analysis of the genetic architecture of T1DM has identified HLA class I and II loci and over 40 non HLA loci associated with the disease. However, a substantial amount of the heritability of T1DM has not been accounted for by conventional genetic analysis.



By using informative families with a high prevalence of T1DM we hope to identify novel susceptibility loci associated with disease. Using combined linkage and association analysis we hope to elucidate the causal genes at these loci, proposing possible mechanisms for their involvement in T1DM.



Using the patient population under the care of Diabetologists at Charing Cross and Hammersmith Hospital, we identified patients with a significant family history of T1DM  (≥1 first degree or ≥2 second degree relatives concordant for disease). Detailed clinical and family history was obtained from these patients. Saliva samples were collected for DNA extraction using Oragene-DNA self-collection kits. Ethical approval was obtained via Imperial College Tissue bank as a sub-collection for Cambridge Bioresource NRES 04/Q0108/44



19 families were identified and detailed family histories were obtained. Families included a family with all male cases, a family with familial aggregation of T1DM and a family with clustering of several autoimmune diseases. Genotyping of the patient cohort is currently awaited. Recruitment is continuing with active participation from Charing Cross Hospital and the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), Addenbrooke’s Hospital. 



This preliminary investigation has identified the potential of studying families with a strong family history of T1DM. A multidisciplinary approach involving endocrinologists, immunologists and geneticists is required to further our understanding of the aetiology behind autoimmune endocrine diseases.