Association Analysis of the Lymphocyte-Specific Protein Tyrosine Kinase (LCK) Gene in Type 1 Diabetes
- John S. Hulme1,
- Bryan J. Barratt1,
- Rebecca C.J. Twells1,
- Jason D. Cooper1,
- Chris E. Lowe1,
- Joanna M.M. Howson1,
- Alex C. Lam1,
- Luc J. Smink1,
- David A. Savage2,
- Dag E. Undlien3,
- Cristian Guja4,
- Constantin Ionescu-Tîırgovişte4,
- Eva Tuomilehto-Wolf5,
- Jaakko Tuomilehto56 and
- John A. Todd1
- 1Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust (WT) Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K
- 2Department of Medical Genetics, Queen’s University Belfast, Belfast City Hospital, Belfast, Northern Ireland
- 3Institute of Medical Genetics, Ulleval University Hospital, University of Oslo, Oslo, Norway
- 4Clinic of Diabetes, Institute of Diabetes, Nutrition, and Metabolic Diseases ‘N. Paulescu’, Bucharest, Romania
- 5Diabetes and Genetic Epidemiology Unit, National Public Health Institute, University of Helsinki, Helsinki, Finland
- 6Department of Public Health, University of Helsinki, Helsinki, Finland
- Address correspondence and reprint requests to Prof. John A. Todd, JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2XY, U.K. E-mail: john.todd{at}cimr.cam.ac.uk
Abstract
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.
- EMBL, European Molecular Biology Laboratory
- LCK, lymphocyte-specific protein tyrosine kinase
- SNP, single nucleotide polymorphism
- UTR, untranslated region
Footnotes
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Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
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- Accepted May 26, 2004.
- Received October 8, 2003.
- DIABETES
