Genetics
The BOA Warren 2 Trios collection represent 'typical' UK Type 2 diabetes who have presented at a younger age as a result of obesity and will aid the identification of type 2 diabetes susceptibility genes in UK Cauca,ians.
Abstract
Major susceptibility genes for Type 2 diabetes have not been described. Case/control association studies frequently result in false positive results as a result of population stratification. The Transmission Disequilibrium Test (TOT) is one of the most robust methods of assessing the role of genes but requires DNA from parents to determine if alleles are preferentially transmitted to affected offspring. This type of study has been considered impossible in Type 2 diabetes due to the late age of onset. We assessed the feasibility of ascertaining a large collection of trios of Type 2 diabetes patient with two living parents. A community based survey revealed that 152/5,807 (2.7%) Caucasian Type 2 diabetics have both parents alive. 186 trios were collected from three UK centres. In 47% of trios had at least one known affected parent. The probands were compared to 882 UK Type 2 subjects with an affected sibling. The trio probands were more obese, CBMI 31.6 ±7.0 v 29.0 ± 5 kgm· 2 mean± SD p<O.OOOI ), diagnosed younger (40.1 ± 6.8 yr. v 55.5 ± 8.7 yr. p<O.OOOI ), but had a similar distribution of treatment requirements (20/61/19 v 18/66/16 %diet/oral agents/insulin NS). The commonest cause of MODY (Cins291) was excluded in all subjects and GAD antibodies were only found in 3%. The BOA Warren 2 Trios collection represent 'typical' UK Type 2 diabetes who have presented at a younger age as a result of obesity. This unique resource will aid the identification of type 2 diabetes susceptibility genes in UK Cauca,ians.