Identification and characterisation of a sequence related to human sorbitol dehydrogenase.

The polyol pathway comprises the enzymes aldose reductase and sorbitol dehydrogenase which convert glucose to fructose via sorbitol. Accumulation of sorbitol within the cell has been suggested to contribute to the progression of secondary complications of diabetes. High levels of sorbitol accumulate within the cell due to inadequate regulation of blood glucose levels. It has also been suggested that polymorphism in either the aldose reductase or sorbitol dehydrogenase genes might contribute to sorbitol accumulation. The human sorbitol dehydrogenase gene (SORD) has been described previously and a range of putative polymorphic variants were identified. Further analysis of human SORD yeast artificial chromosome clones has now shown that there is a second SORD-like sequence in man, which is extremely similar in sequence to SORD itself and which also maps to chromosome 15. Detailed sequence analysis suggests that this SORD-related gene cannot be expressed as a full-length sorbitol dehydrogenase isoenzyme. However, knowledge of the presence of this highly similar sequence in the human genome is essential to ensure that sequence variations identified during genetic analysis of SORD are not attributed to polymorphisms within that gene itself.