Method for determining susceptibility to heart disease by screening polymorphisms in the vitamin D receptor gene

Abstract

The present invention relates to prognostic method and means for determining susceptibility to heart disease in a subject by screening for polymorphisms in the Vitamin D receptor gene. In particular, the present invention provides a method for determining susceptibility to heart disease, the method comprising analysing the genetic material of a subject to determine which of the B/b, A/a or T/t alleles of the restriction enzyme sites BsmI, ApaI and TaqI respectively are present. Specific combinations of alleles represent a haplotype which is associated with susceptibility to heart disease.

1 . A method of determining susceptibility to heart disease in a subject, said method comprising analysing genetic material of a subject to determine which of the B/b, A/a or T/t alleles of the BsmI, ApaI or TaqI sites of the vitamin D receptor gene is/are present, wherein the b, a or T allele(s) are associated with risk of heart disease.  
     
     
         2 . A method of determining susceptibility to heart disease according to  claim 1 , said method comprising analysing the genetic material of a subject to determine the haplotype of the BsmI, ApaI or TaqI alleles of the vitamin D receptor.  
     
     
         3 . A method according to  claim 2  wherein the haplotype may be determined by amplification of a relevant portion of the vitamin D receptor gene, followed by restriction enzyme digestion.  
     
     
         4 . A method of determining susceptibility to heart disease according to  claim 1 ,  2 , or  3 , said method comprising determining the copy number of the B/b, A/a or T/t alleles or haplotype of the vitamin D receptor.  
     
     
         5 . A method according to  claim 1 , further comprising determining whether the allele(s) present is/are associated with risk of heart disease.  
     
     
         6 . A method according to  claim 5  comprising comparing the allele(s) present in the genetic material of the subject with those known to be associated allele(s) of vitamin D receptor genotypes having known degree of risk of heart disease.  
     
     
         7 . A method according to  claim 1  wherein said method further comprises determining aspects of calcium metabolism in a subject.  
     
     
         8 . A method according to  claim 7 , wherein daily calcium intake of a subject is measured.  
     
     
         9 . A method according to  claim 1  wherein said method is performed in vitro.  
     
     
         10 . A method according to  claim 9  wherein said method is performed on blood or tissue samples of a subject.  
     
     
         11 . A method according to  claim 1  wherein the subject is a mammal.  
     
     
         12 . A method according to  claim 11  wherein the subject is a human.  
     
     
         13 . A method according to  claim 11  or  12  wherein the subject is male.  
     
     
         14 . A method according to  claim 1  for determining susceptibility of a subject to atrial or ventricular hypertrophy, aortic calcification, myocardial infarction, or hypertension.  
     
     
         15 . A method according to  claim 1 , further comprising treating the subject to reduce the risk of heart disease.  
     
     
         16 . A method according to  claim 15  wherein said treatment is selected from the group of treatments consisting of modifications to lifestyle, regular exercise, changes in diet and pharmaceutical preparations.  
     
     
         17 - 22 . (canceled).