Genetic polymorphisms associated with coronary stenosis, methods of detection and uses thereof

Abstract

The present invention is based on the discovery of genetic polymorphisms that are associated with coronary stenosis. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acids and proteins as well as methods of using reagents for their detection.

1 . A method of identifying a human having an altered risk for coronary stenosis, comprising detecting the presence of a single nucleotide polymorphism (SNP) at position 101 of SEQ ID NO: 41 or its complement thereof in said human's nucleic acids, wherein the presence of G at position 101 of SEQ ID NO: 41 is indicative of an increased risk for coronary stenosis, or the presence of A at position 101 of SEQ ID NO: 41 is indicative of a decreased risk for coronary stenosis.  
     
     
         2 . The method of  claim 1  wherein SEQ ID NO: 41 is a segment within the genomic sequence of CD163 gene as represented by SEQ ID NO: 37.  
     
     
         3 . The method of  claim 1  wherein the SNP is located at position 24287 of SEQ ID NO: 37.  
     
     
         4 . The method of  claim 1  wherein said human's nucleic acids are extracted from a biological sample therefrom.  
     
     
         5 . The method of  claim 1  wherein said human's nucleic acids are amplified before being detected.  
     
     
         6 . The method of  claim 1  wherein the detecting is carried out by using detection reagents comprising the nucleotide sequences of SEQ ID NO: 51, SEQ ID NO: 52, and SEQ ID NO: 53.  
     
     
         7 . The method of  claim 1  in which the detecting is carried out by a process selected from the group consisting of: allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism.  
     
     
         8 . A method of identifying a human having an increased risk for coronary stenosis, comprising detecting the presence of a single nucleotide polymorphism (SNP) at position 101 of SEQ ID NO: 41 or its complement thereof in said human's nucleic acids, wherein the presence of G at position 101 of SEQ ID NO: 41 is indicative of an increased risk for coronary stenosis.  
     
     
         9 . The method of  claim 8  wherein SEQ ID NO: 41 is a segment within the genomic sequence of CD163 gene as represented by SEQ ID NO: 37.  
     
     
         10 . The method of  claim 8  wherein the SNP is located at position 24287 of SEQ ID NO: 37.  
     
     
         11 . The method of  claim 8  wherein said human's nucleic acids are extracted from a biological sample therefrom.  
     
     
         12 . The method of  claim 8  wherein said human's nucleic acids are amplified before being detected.  
     
     
         13 . The method of  claim 8  wherein the detecting is carried out by using detection reagents comprising the nucleotide sequences of SEQ ID NO: 51, SEQ ID NO: 52, and SEQ ID NO: 53.  
     
     
         14 . The method of  claim 8  in which the detecting is carried out by a process selected from the group consisting of: allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism.  
     
     
         15 . A method of identifying a human having a decreased risk for coronary stenosis, comprising detecting the presence of a single nucleotide polymorphism (SNP) at position 101 of SEQ ID NO: 41 or its complement thereof in said human's nucleic acids, wherein the presence of A at position 101 of SEQ ID NO: 41 is indicative of a decreased risk for coronary stenosis.  
     
     
         16 . The method of  claim 15  wherein SEQ ID NO: 41 is a segment within the genomic sequence of CD163 gene as represented by SEQ ID NO: 37.  
     
     
         17 . The method of  claim 15  wherein the SNP is located at position 24287 of SEQ ID NO: 37.  
     
     
         18 . The method of  claim 15  wherein said human's nucleic acids are extracted from a biological sample therefrom.  
     
     
         19 . The method of  claim 15  wherein said human's nucleic acids are amplified before being detected.  
     
     
         20 . The method of  claim 15  wherein the detecting is carried out by using detection reagents comprising the nucleotide sequences of SEQ ID NO: 51, SEQ ID NO: 52, and SEQ ID NO: 53.  
     
     
         21 . The method of  claim 15  in which the detecting is carried out by a process selected from the group consisting of: allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism.  
     
     
         22 . A method of determining a human's risk for developing coronary stenosis, comprising detecting the presence of a single nucleotide polymorphism (SNP) at position 101 of SEQ ID NO: 41 or its complement thereof in said human's nucleic acids, wherein the presence of G at position 101 of SEQ ID NO: 41 is indicative of an increased risk for developing coronary stenosis in said human, or the presence of A at position 101 of SEQ ID NO: 41 is indicative of a decreased risk for developing coronary stenosis in said human.  
     
     
         23 . The method of  claim 22  wherein said human's nucleic acids are amplified before being detected.  
     
     
         24 . The method of  claim 22  wherein the detecting is carried out by using detection reagents comprising the nucleotide sequences of SEQ ID NO: 51, SEQ ID NO: 52, and SEQ ID NO: 53.  
     
     
         25 . The method of  claim 22  in which the detecting is carried out by a process selected from the group consisting of: allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism.