Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in type 1 diabetes.
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.
Hulme
John S
JS
JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK.
Barratt
Bryan J
BJ
Twells
Rebecca C J
RC
Cooper
Jason D
JD
Lowe
Chris E
CE
Howson
Joanna M M
JM
Lam
Alex C
AC
Smink
Luc J
LJ
Savage
David A
DA
Undlien
Dag E
DE
Guja
Cristian
C
Ionescu-Tîirgoviste
Constantin
C
Tuomilehto-Wolf
Eva
E
Tuomilehto
Jaakko
J
Todd
John A
JA
D000328:Adult; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)