Genetic markers family history and birth weight

Family clustering of diabetic renal disease suggests that genetic factors could be important in determining so-called susceptibility to nephropathy [66-73]. In some studies, diabetic siblings of probands with type 1 diabetes had a prevalence of diabetic nephropathy. Taking this fact into consideration, along with a cumulative incidence of diabetic renal disease in the siblings of diabetic patients that is as high as 70% versus 25% in siblings of probands without renal disease, again suggested a possible genetic background for renal disease in diabetes [73].

Several genes have been proposed as biologically interesting candidates for the so-called 'nephropathy gene'. Polymorphisms of the angiotensin converting enzyme, the so-called I-D-genotype, have been proposed, and the angiotensinogen gene and angiotensin II type 1 receptor gene have also been suggested. The I-D genotype has been examined in various populations in addition to other genes, e.g. the aldoreductase gene and lipid-related genes [66, 74].

So far, examination of these candidate genes in case-controlled studies has produced very conflicting results. However, it may well be that larger studies using new strategies such as family-based association studies of linkage analysis of sibpairs might give better information, although this is still unknown. In fact, a key point may be that the main determinants of diabetic renal disease are still poor glycaemic control and increased blood pressure. These two factors especially, considered together, seem to be major determinants of diabetic renal disease. So far, genetic analysis has found no place in the clinical management of diabetic patients and cannot be used as a biomarker for renal disease. The role of low birth weight and related parameters is also uncertain [1, 75, 76].

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