title: L-selectin gene T668C mutation in type 1 diabetes patients and their first degree relatives.
abstract: There have been some studies published recently which have suggested that L-selectin and/or other adhesion molecules could be the new markers for diabetes type 1 risk development in humans and animal models of the disease. The alterations of soluble L-selectin have been found not only in overt but also in the preclinical stage of disease development and were independent from the presence of ICA - a marker of ongoing autoimmunity, but associated with HLA related genetic predisposition to insulin-dependent diabetes mellitus (IDDM). The aim of our study was to evaluate the frequency of the L-selectin gene T668C mutation (from thymine to cytosine at position 668) resulted in F206L an amino acid substitution in patients with overt diabetes and their unaffected first degree relatives in comparison to the unselected control population. In the unaffected siblings of IDDM subjects we have observed a significantly higher frequency of the L-selectin gene T668C mutation in comparison to their relatives with type 1 diabetes and healthy controls. It was also shown that there is an association between T668C mutation and low HLA related risk of IDDM development, the highest frequency of F206L mutation in the EGF domain of L-selectin was observed in relatives with 'protective' HLA DQB1*0602 allele and nonDRB1*03-nonDRB1*04 haplotype, while in subjects 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 of IDDM, but further studies concerning their role in type 1 diabetes are needed.
authors.affiliation: Department of Endocrinology, Medical School Biatystok, U1 M.C. Skl&z. shtsls;odowska-Curie 24 a, 15-267, Bial&z.shtsls;ystok, Poland. akretows@amb.ac.bialystok.pl
authors.forename: A
authors.initials: A
authors.lastname: Kretowski
authors.forename: I
authors.initials: I
authors.lastname: Kinalska
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D003062:Codon / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019041:L-Selectin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D010290:Parents; D017354:Point Mutation
chemical_list: D003062:Codon; D006680:HLA Antigens; D019041:L-Selectin