title: No association between lck gene polymorphisms and protein level in type 1 diabetes.
abstract: We previously described a reduced expression of the protein tyrosine kinase Lck in T-cells from type 1 diabetic patients, the origin of which is still unknown. The human lck gene, located on chromosome 1p35-34.3, was evaluated as a candidate susceptibility gene for type 1 diabetes. A molecular scan of the sequence variations in the coding, the relevant promoter, and most of the intronic sequences of the lck gene (representing a total of 10.5 kb fragment) was performed in 187 Caucasian subjects including 91 type 1 diabetic patients and 96 normoglycemic control subjects. We identified 35 sequence variations, including one deletion and 34 single nucleotide polymorphisms (SNPs), 33 of them being new. Four variants were frequent but not significantly associated with diabetes or Lck protein level. Of the SNP variants, 11 were only found within the diabetic population and some were associated with low Lck protein levels. The low frequency of these polymorphisms did not permit any statistically significant correlations with the disease status, suggesting that the lck gene probably does not contribute to genetic susceptibility to type 1 diabetes.
authors.affiliation: Université de la Méditerranée, CHU Sainte-Marguerite, Marseille, France.
authors.forename: Solange
authors.initials: S
authors.lastname: Nervi
authors.forename: Sandra
authors.initials: S
authors.lastname: Nicodeme
authors.forename: Corinne
authors.initials: C
authors.lastname: Gartioux
authors.forename: Catherine
authors.initials: C
authors.lastname: Atlan
authors.forename: Marc
authors.initials: M
authors.lastname: Lathrop
authors.forename: Denis
authors.initials: D
authors.lastname: Reviron
authors.forename: Philippe
authors.initials: P
authors.lastname: Naquet
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Jean
authors.initials: J
authors.lastname: Imbert
authors.forename: Bernard
authors.initials: B
authors.lastname: Vialettes
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005602:France; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D044465:White People
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)