Method of detecting risk of type II diabetes based on mutations found in carboxypeptidase E

Abstract

The invention is directed to methods for diagnosing Type II diabetes or the risk for developing Type II diabetes by detecting alterations in expression, sequence, or function of carboxypeptidase E nucleic acid or protein. The invention is also directed to methods for preventing or treating Type II diabetes by modulating the levels, altering the sequence, or controlling the function of carboxypeptidase E nucleic acid or protein. The invention is also directed to methods for identifying agents that modulate the levels or affect the function of carboxypeptidase E nucleic acid or protein. The invention is also directed to methods using the agents to treat or diagnose Type II diabetes. The invention is also directed to animal models of Type II diabetes using the carboxypeptidase E gene. The invention is also directed to compositions based on carboxypeptidase E nucleic acid or protein useful for treating or diagnosing diabetes, identifying compounds for treating or diagnosing diabetes, and developing animal models of diabetes.

That which is claimed:  
     
         1 . A method for detecting a mutation in the CPE gene or gene product in a human subject having, or predisposed to having, Type II diabetes, said method comprising: 
 (a) obtaining a biological sample from a subject having, or predisposed to having, Type II diabetes, said sample containing a CPE gene or gene product; and    (b) detecting an alteration in said CPE gene or gene product by means of an assay that allows detection of said alteration in combination with an increase or decrease in the level of carboxypeptidase E gene expression in a patient compared to a control subject.    
     
     
         2 . A method of diagnosing Type II diabetes or predisposition to having Type II diabetes in a human subject, said method comprising: 
 (a) obtaining a biological sample from said subject, said sample containing carboxypeptidase E gene or gene product;    (b) identifying an alteration in carboxypeptidase E gene or gene product by means of an assay that allows detection of said alteration in combination with an increase or decrease in the level of carboxypeptidase E gene expression in a patient compared to a control subject; and    (c) correlating said alteration with Type II diabetes or the predisposition for developing Type II diabetes in said subject.    
     
     
         3 . A method for determining whether a human subject has or is at risk for developing type II diabetes comprising the steps of: 
 (a) obtaining a sample from a subject, said sample comprising nucleic acid molecules containing a carboxypeptidase E (CPE) gene; and    (b) detecting the presence or absence of a genetic mutation in the gene of said subject, wherein said genetic mutation comprises an alteration in the codon which codes for amino acid 283 which results in a replacement of arginine by another amino acid and the presence of said genetic mutation identifies a subject that has or is at risk for developing type II diabetes.    
     
     
         4 . The method according to    claim 3   , wherein the arginine is replaced by the amino acid tryptophan.  
     
     
         5 . A method for determining whether a human subject has or is at risk for developing type II diabetes comprising the steps of: 
 (a) obtaining a sample from a subject, said sample comprising nucleic acid molecules containing a carboxypeptidas E (CPE) gene; and    (b) detecting the presence or absence of a genetic mutation in the gene of said subject, wherein said genetic mutation comprises an alteration in the codon beginning at nucleotide 1133, which results in a replacement of arginine by another amino acid.    
     
     
         6 . The method according to    claim 4   , wherein the arginine is replaced by the amino acid tryptophan.  
     
     
         7 . A method for determining whether a subject has or is at risk for developing type II diabetes comprising the steps of: 
 (a) obtaining a sample from a subject, said sample comprising nucleic acid molecules containing a carboxypeptidas E (CPE) gene; and    (b) determining the copy number of said CPE gene compared to a control subject.    
     
     
         8 . A method for determining whether a subject has or is at risk for developing type II diabetes comprising the steps of: 
 (a) obtaining a sample from a subject, said sample comprising nucleic acid molecules containing a carboxypeptidas E (CPE) gene; and    (b) identifying an alteration in carboxypeptidase E (CPE) gene by means of an assay that allows detection of an alteration in said gene wherein said alteration is selected from the group consisting of: an insertion, a deletion, a point mutation, and an inversion in said gene.    
     
     
         9 . A method for determining whether a subject has or is at risk for developing type II diabetes comprising the steps of: 
 (a) obtaining a sample from a subject, said sample comprising nucleic acid molecules containing a carboxypeptidase E (CPE) gene; and    (b) identifying a gross rearrangement of said CPE gene in the genome of said subject using in situ hybridization.