cDNA for human methylenetetrahydrofolate reductase

Abstract

Provided herein is a heretofore unknown isolated nucleic acid molecule which encodes human methylenetetrahydrofolate reducatase, along with an amino acid sequence of methylenetetrahydrofolate reductase, and a cDNA probe for human methylenetetrahydrofolate reductase. Also provided are a molecule description of mutations in humans resulting in a phenotype having reduced levels of methylenetetrahydrofolate reductase, and methods of diagnosing methylenetetrahydrofolate reductase deficiency in a human.

1 . A method for treating an individual having an MTHFR allele variant correlated to increased or decreased toxicity of a treatment, said method comprising: 
 (a) analyzing a nucleic acid sample obtained from said individual to determine whether said sample comprises at least one MTHFR allele variant, said variant leading to a decrease in MTHFR activity, and said variant being correlated to increased or decreased toxicity to a treatment for a disorder selected from the group consisting of cardiovascular disorders, coronary and arterial disorders, osteoporosis, and neurological disorders; and    (b) administering said treatment to said individual having said MTHFR allele variant.    
     
     
         2 . A method for treating an individual having an MTHFR allele variant correlated to increased or decreased toxicity of a treatment, said method comprising: 
 (a) analyzing a nucleic acid sample obtained from said individual to determine whether said sample comprises at least one MTHFR allele variant, said variant leading to a decrease in MTHFR activity, and said variant being correlated to increased or decreased toxicity to a treatment selected from the group consisting of antibiotics and antiepileptic agents; and    (b) administering said treatment to said individual having said MTHFR allele variant.    
     
     
         3 . A method for selecting a treatment that has increased or decreased toxicity in an individual having an MTHFR allele variant, said method comprising: 
 (a) analyzing a nucleic acid sample obtained from said individual to determine whether said sample comprises at least one MTHFR allele variant, said variant leading to a decrease in MTHFR activity, and said variant being correlated to increased or decreased toxicity to a treatment for a disorder selected from the group consisting of cardiovascular disorders, coronary and arterial disorders, osteoporosis, and neurological disorders; and    (b) selecting a treatment known to have increased or decreased drug toxicity in an individual having said MTHFR allele, wherein said treatment is for a disorder selected from the group consisting of cardiovascular disorders, coronary and arterial disorders, osteoporosis, and neurological disorders.    
     
     
         4 . A method for selecting a treatment that has increased or decreased toxicity in an individual having an MTHFR allele variant, said method comprising: 
 (a) analyzing a nucleic acid sample obtained from said individual to determine whether said sample comprises at least one MTHFR allele variant, said variant leading to a decrease in MTHFR activity, and said variant being correlated to increased or decreased toxicity to a treatment selected from the group consisting of antibiotics and antiepileptic agents; and    (b) selecting a treatment known to have increased or decreased drug toxicity in an individual having said MTHFR allele, wherein said treatment is selected from the group consisting of antibiotics and antiepileptic agents.    
     
     
         5 . The method of  claim 1  or  2 , wherein said treatment affects folate metabolism and leads to an increased level of folate or to a decreased level of homocysteine.  
     
     
         6 . The method of  claim 1  or  2 , wherein said treatment is for a disorder associated with reduced MTHFR activity.  
     
     
         7 . The method of  claim 1  or  2 , wherein said treatment is for a disorder associated with said MTHFR allele variant.  
     
     
         8 . The method of  claim 1  or  2 , wherein said MTHFR allele variant is associated with a disorder influenced by folic acid metabolism.  
     
     
         9 . The method of  claim 1  or  3 , wherein said disorder is a neural tube defect.  
     
     
         10 . The method of  claim 1  or  2 , wherein said MTHFR allele variant correlates with increased drug responsiveness to said a treatment, and wherein said treatment affects folate metabolism and leads to an increased level of folate or to a decreased level of homocysteine.  
     
     
         11 . The method of  claim 1  or  2 , further comprising administering folate or folic acid to said individual.  
     
     
         12 . The method of  claim 1  or  2 , wherein said MTHFR allele variant is selected from the group consisting of 167G/A, 482G/A, 559C/T, 677C/T, 692C/T, 764C/T, 792+1G/A, 985C/T, 1015C/T, and 1081C/T.  
     
     
         13 . The method of  claim 12 , wherein said MTHFR allele variant is 677C/T.  
     
     
         14 . A method for identifying an individual having an MTHFR allele variant correlated to increased or decreased toxicity of a treatment, said method comprising analyzing a nucleic acid sample obtained from an individual to determine whether said sample comprises at least one MTHFR allele variant correlated to increased or decreased toxicity of a treatment for a disorder selected from the group consisting of cardiovascular disorders, coronary and arterial disorders, osteoporosis, and neurological disorders, wherein said MTHFR allele variant leads to a decrease in MTHFR activity.  
     
     
         15 . A method for identifying an individual having an MTHFR allele variant correlated to increased or decreased toxicity of a treatment, said method comprising analyzing a nucleic acid sample obtained from an individual to determine whether said sample comprises at least one MTHFR allele variant correlated to increased or decreased toxicity of a treatment selected from the group consisting of antibiotics and antiepileptic agents, wherein said MTHFR allele variant leads to a decrease in MTHFR activity.