L-selectin gene T668C mutation in type 1 diabetes patients and their firstdegree relatives

There have been some studies published recently which have suggested that L -selectin and/or other adhesion molecules could be the new markers for diab etes type 1 risk development in humans and animal models of the disease. Th e alterations of soluble L-selectin have been found not only in overt but a lso in the preclinical stage of disease development and were independent fr om the presence of ICA - a marker of ongoing autoimmunity, but associated w ith HLA related genetic predisposition to insulin-dependent diabetes mellit us (IDDM). The aim of our study was to evaluate the frequency of the L-sele ctin gene T668C mutation (from thymine to cytosine at position 668) resulte d in F206L an amino acid substitution in patients with overt diabetes and t heir unaffected first degree relatives in comparison to the unselected cont rol population. In the unaffected siblings of IDDM subjects we have observe d a significantly higher frequency of the L-selectin gene T66SC mutation in comparison to their relatives with type 1 diabetes and healthy controls. I t was also shown that there is an association between T668C mutation and lo w HLA related risk of IDDM development, the highest frequency of F206L muta tion in the EGF domain of L-selectin was observed in relatives with 'protec tive' HLA DQB1*0602 allele and nonDRB1*03-nonDRB1*04 haplotype, while in su bjects with highest risk of IDDM haplotype the frequency of T668C mutation was similar to the controls. We would like to hypothesise that the T668C L- selectin gene mutation could have a (protective?) role in the development o f IDDM, but further studies concerning their role in type 1 diabetes are ne eded. (C) 2000 Elsevier Science B.V. All rights reserved.