Association of protein kinase C zeta polymorphisms with diabetes

Abstract

A central role for the gene encoding protein kinase C zeta in diabetes and perhaps in related disorders is disclosed. Use of single nucleotide polymorphisms in the protein kinase C zeta gene for diagnosis, prediction of clinical course and treatment response, development of new treatments and development of cell-culture based and animal models for research and treatment are disclosed.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule comprising at least 500 contiguous nucleotides of the nucleic acid sequence of SEQ ID NO: 1, wherein the isolated nucleic acid molecule comprises nucleotide position 246 of SEQ ID NO: 1 which is occupied by a cytosine (C), and the complement of said isolated nucleic acid molecule.  
     
     
         2 . An expression vector comprising the isolated nucleic acid molecule according to  claim 1 .  
     
     
         3 . A host cell comprising the expression vector of  claim 2 .  
     
     
         4 . An oligonucleotide microarray having immobilized thereon a plurality of probes, wherein at least one of said probes is specific for an isolated nucleic acid molecule comprising at least 500 contiguous nucleotides of the nucleic acid sequence of SEQ ID NO: 1, wherein the isolated nucleic acid molecule comprises nucleotide position 246 of SEQ ID NO: 1 which is occupied by a cytosine (C), and wherein the probe hybridizes to a portion of the isolated nucleic acid molecule comprising nucleotide position 246 of SEQ ID NO: 1.  
     
     
         5 . An isolated nucleic acid molecule which specifically hybridizes under conditions of high stringency to a second isolated nucleic acid molecule comprising at least 500 contiguous nucleotides of the nucleic acid sequence of SEQ ID NO: 1, wherein the second isolated nucleic acid molecule comprises nucleotide position 246 of SEQ ID NO: 1 which is occupied by a cytosine (C), and wherein the isolated nucleic acid molecule hybridizes to a portion of the second isolated nucleic acid molecule comprising nucleotide position 246 of SEQ ID NO: 1.  
     
     
         6 . A kit for diagnosis of diabetes comprising one or more allele-specific oligonucleotides that hybridize to a nucleic acid molecule comprising all or a portion of the nucleic acid sequence of SEQ ID NO: 1 wherein said nucleic acid molecule is at least 10 nucleotides in length and wherein the nucleic acid sequence comprises nucleotide position 246 of SEQ ID NO: 1 which is occupied by a cytosine (C).  
     
     
         7 . A kit according to  claim 6 , wherein the allele-specific oligonucleotides are contained on a microarray.  
     
     
         8 . A kit according to  claim 6 , wherein said kit further comprises a written instruction sheet.