Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in type 1 diabetes
Hulme JS., Barratt BJ., Twells RCJ., Cooper JD., Lowe CE., Howson JMM., Lam AC., Smink LJ., Savage DA., Undlien DE., Guja C., Ionescu-Tîrgovişte C., Tuomilehto-Wolf E., Tuomilehto J., Todd JA.
Prior data associating the expression of lymphocyte-specific protein tyrosine kinase (LCK) with type 1 diabetes, its critical function in lymphocytes, and the linkage of the region to diabetes in the nonobese diabetic (NOD) mouse model make LCK a premier candidate for a susceptibility gene. Resequencing of LCK in 32 individuals detected seven single nucleotide polymorphisms (SNPs) with allele frequencies >3%, including four common SNPs previously reported. These and six other SNPs from dbSNP were genotyped in a two-stage strategy using 2,430 families and were all shown not to be significantly associated with type 1 diabetes. We conclude that a major role for the common LCK polymorphisms in type 1 diabetes is unlikely. However, we cannot rule out the possibility of there being a causal variant outside the exonic, intronic, and untranslated regions studied.