Methods for analyzing LTC4 synthase polymorphisms and diagnostic use

Abstract

This invention relates to single nucleotide polymorphisms in the LTC 4 synthase gene, EMBL accession no. U50136, particularly at one or more of positions 375, 815, 1003, 2169 and 2742. The invention also relates to methods and materials for analysing allelic variation in the LTC 4 synthase gene, and to the use of LTC 4 synthase polymorphism in the diagnosis and treatment of leukotriene mediated diseases such as asthma and allergic rhinitis.

1 . A method for the diagnosis of a single nucleotide polymorphism in LTC 4  synthase in a human, which method comprises determining the sequence of the nucleic acid of the human at one or more of positions 375, 815, 1003, 2169 and 2742 in the LTC 4  synthase gene as defined by the positions in SEQ ID NO: 1, and determining the status of the human by reference to polymorphism in the LTC 4  synthase gene.  
     
     
         2 . A method according to  claim 1  in which the single nucleotide polymorphism at position 375 is presence of G and/or A.  
     
     
         3 . A method according to  claim 1  in which the single nucleotide polymorphism at position 815 is presence of C and/or A.  
     
     
         4 . A method according to  claim 1  in which the single nucleotide polymorphism at position 1003 is presence of A and/or C.  
     
     
         5 . A method according to  claim 1  in which the single nucleotide polymorphism at position 2169 is presence of C and/or T.  
     
     
         6 . A method according to  claim 1  in which the single nucleotide polymorphism at position 2742 is presence of C and/or T.  
     
     
         7 . A method according to any one of claims  1 - 6  in which the sequence is determined by a method selected from amplification refractory mutation system and restriction fragment length polymorphism.  
     
     
         8 . A nucleic acid comprising the 5′ untranslated region of LTC 4  synthase comprising a polymorphism corresponding with one or more of positions 375, 815 and 1003 as defined by the positions in SEQ ID NO: 1 and in which there is an A at position 375, an A at position 815 and a C at position 1003.  
     
     
         9 . A nucleic acid comprising the first intron of the LTC 4  synthase gene comprising a polymorphism at one or more of positions 2169 and 2742 as defined by the position in SEQ ID NO: 1 and in which there is a T at position 2169 and there is a T at position 2742.  
     
     
         10 . A diagnostic nucleic acid primer capable of detecting a LTC 4  synthase gene polymorphism at one or more of positions 375, 815, 1003, 2169 and 2742 in the LTC 4  synthase gene as defined by the positions in SEQ ID NO: 1.  
     
     
         11 . An allele-specific oligonucleotide probe capable of detecting a LTC 4  synthase gene polymorphism at one or more of positions 375, 815, 1003, 2169 and 2742 in the LTC 4  synthase gene as defined by the positions in SEQ ID NO: 1.  
     
     
         12 . A diagnostic kit comprising a diagnostic primer as defined in  claim 10  and/or an allele-specific oligonucleotide primer as defined in  claim 11 .  
     
     
         13 . A method of treating a human in need of treatment with an antileukotriene drug in which the method comprises: 
 i) diagnosis of a single nucleotide polymorphism in LTC 4  synthase in the human, which diagnosis comprises determining the sequence of the nucleic acid at one or more of positions 375, 815, 1003, 2169 and 2742 in the LTC 4  synthase gene as defined by the positions in SEQ ID NO: 1, and determining the status of the human by reference to polymorphism in the LTC 4  synthase gene; and    ii) administering an effective amount of an antileukotriene drug.    
     
     
         14 . Use of an antileukotriene drug in preparation of a medicament for treating a leukotriene mediated disease in a human diagnosed as having a single nucleotide polymorphism at one or more of positions 375, 815, 1003, 2169 and 2742 in LTC 4  synthase gene as defined by the positions in SEQ ID NO: 1.