Methods for Detecting an increased risk for coronary heart disease

Abstract

The invention relates generally to an allele on human chromosome 9 associated with increased risk for coronary heart disease and the use or detection of such an allele in determining whether a human has an increased risk for coronary heart disease. In one aspect, the invention relates to methods for detecting a predisposition or propensity or susceptibility for coronary heart disease in a human, comprising detecting the presence of an allele on human chromosome 9 that is associated with an increased risk for coronary heart disease in a human. Disclosed are methods and compositions for determining whether a person carries an allele associated with increased risk for coronary atherosclerosis by determining whether the person has an RA-CHR9 allele, such as by determining whether the person has an RA-CHR9 allele-associated single nucleotide polymorphism (SNP). The invention also relates to kits for detecting the presence of an allele on chromosome 9 associated with an increased risk for coronary heart disease.

1 - 30 . (canceled) 
     
     
         31 . A method for identifying a human subject at increased risk for coronary heart disease, comprising using an in vitro assay to detect the presence in the subject of a genetic marker associated with increased risk for coronary heart disease in a population, and assigning to the subject an increased risk for coronary heart disease according to the presence of the marker,
 wherein the marker is a polymorphism with a linkage disequilibrium in the population of at least r 2 =0.50 with at least one “G” allele at the polymorphic position defined by rs10757274 in a human subject.   
     
     
         32 . The method of  claim 31 , wherein:
 a) the human subject is heterozygous for the polymorphism,   b) the human subject is homozygous for the polymorphism,   c) the linkage disequilibrium has an r 2  of at least 0.8, or   d) the linkage disequilibrium has an r 2  of at least 0.89.   
     
     
         33 . The method of  claim 31 , wherein the coronary heart disease is a myocardial infarction or coronary atherosclerosis or premature coronary heart disease with onset before the age of 60 years. 
     
     
         34 . The method of  claim 31 , wherein the polymorphism is detected using mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR or sequencing. 
     
     
         35 . The method of  claim 31 , wherein the polymorphism comprises at least one of the following: a cytosine at rs9632884, a thymine at rs6475606, a thymine at rs10757272, a guanine at rs4977574, a guanine at rs2891168, a guanine at rs1333042, a cytosine at rs1333048, or a cytosine at rs1333049. 
     
     
         36 . The method of  claim 31 , wherein the polymorphism comprises at least one of the following positions on human chromosome 9 as defined by NCBI Build 36.1 Coordinates: a guanine at position 22062264; a cytosine at position 22062301; an adenine at position 22062638; a guanine at position 22062719; a thymine at position 22071397; a thymine at position 22071850; a thymine at position 22078090; a guanine at position 22078094; a thymine at position 22078260; a deletion at position 22078465; a guanine at position 22088574; a guanine at position 22088619; an insertion at position 22089755; a cytosine at position 22090176; a cytosine at position 22091702; a thymine at position 22092165; a thymine at position 22093183; a guanine at position 22093341; a guanine at position 22093813; a cytosine at position 22095927; an adenine at position 22096731; a cytosine at position 22100131; an insertion at position 22101587; a cytosine at position 22102241; a guanine at position 22102427; a cytosine at position 22104469; a guanine at position 22104495; a cytosine at position 22105286; a guanine at position 22106046; a cytosine at position 22106220; an insertion at position 22110491; a cytosine at position 22113766; an adenine at position 22114123; a thymine at position 22114140; a cytosine at position 22115347; or a cytosine at position 22115503. 
     
     
         37 . A method for detecting susceptibility for coronary heart disease in a human, comprising detecting in a nucleic acid sample isolated from the human the presence of a genetic marker associated with increased risk for coronary heart disease in a population, and assigning to the subject an increased risk for coronary heart disease according to the presence of the marker,
 wherein the marker is at least one “G” allele at the polymorphic position defined by rs10757274, or a single nucleotide polymorphism in linkage disequilibrium in the population of at least r 2 =0.50 with said allele.   
     
     
         38 . The method of  claim 37 , wherein:
 a) the human subject is heterozygous for the polymorphism,   b) the human subject is homozygous for the polymorphism,   c) the linkage disequilibrium has an r 2  of at least 0.8, or   d) the linkage disequilibrium has an r 2  of at least 0.89.   
     
     
         39 . The method of  claim 31 , wherein the coronary heart disease is a myocardial infarction or coronary atherosclerosis or premature coronary heart disease with onset before the age of 60 years. 
     
     
         40 . The method of  claim 37 , wherein the allele is detected using mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR or sequencing. 
     
     
         41 . The method of  claim 37 , wherein the polymorphism comprises at least one of the following: a cytosine at rs9632884, a thymine at rs6475606, a thymine at rs10757272, a guanine at rs4977574, a guanine at rs2891168, a guanine at rs1333042, a cytosine at rs1333048, or a cytosine at rs1333049. 
     
     
         42 . The method of  claim 37 , wherein the polymorphism comprises at least one of the following positions on human chromosome 9 as defined by NCBI Build 36.1 Coordinates: a guanine at position 22062264; a cytosine at position 22062301; an adenine at position 22062638; a guanine at position 22062719; a thymine at position 22071397; a thymine at position 22071850; a thymine at position 22078090; a guanine at position 22078094; a thymine at position 22078260; a deletion at position 22078465; a guanine at position 22088574; a guanine at position 22088619; an insertion at position 22089755; a cytosine at position 22090176; a cytosine at position 22091702; a thymine at position 22092165; a thymine at position 22093183; a guanine at position 22093341; a guanine at position 22093813; a cytosine at position 22095927; an adenine at position 22096731; a cytosine at position 22100131; an insertion at position 22101587; a cytosine at position 22102241; a guanine at position 22102427; a cytosine at position 22104469; a guanine at position 22104495; a cytosine at position 22105286; a guanine at position 22106046; a cytosine at position 22106220; an insertion at position 22110491; a cytosine at position 22113766; an adenine at position 22114123; a thymine at position 22114140; a cytosine at position 22115347; or a cytosine at position 22115503. 
     
     
         43 . A method of genotyping a nucleic acid sample isolated from a human diagnosed as at risk for coronary heart disease, or diagnosed with coronary heart disease, comprising determining in the sample the presence or absence of a genetic marker associated with increased risk for coronary heart disease in a population, wherein the marker is at least one “G” allele at the polymorphic position defined by rs10757274, or a single nucleotide polymorphism that is in linkage disequilibrium in the population with said allele, wherein the linkage disequilibrium has an r 2  of at least 0.50. 
     
     
         44 . The method of  claim 43 , wherein:
 a) the human subject is heterozygous for the polymorphism,   b) the human subject is homozygous for the polymorphism,   c) the linkage disequilibrium has an r 2  of at least 0.8, or   d) the linkage disequilibrium has an r 2  of at least 0.89.   
     
     
         45 . The method of  claim 43 , wherein the coronary heart disease is a myocardial infarction or coronary atherosclerosis or premature coronary heart disease with onset before the age of 60 years. 
     
     
         46 . The method of  claim 43 , wherein the genotyping is performed using allele-specific hybridization, allele-specific primer extension, allele-specific PCR, sequencing, single-stranded conformation polymorphisms detection, or molecular beacon assay. 
     
     
         47 . The method of  claim 43 , wherein the polymorphism comprises at least one of the following: a cytosine at rs9632884, a thymine at rs6475606, a thymine at rs10757272, a guanine at rs4977574, a guanine at rs2891168, a guanine at rs1333042, a cytosine at rs1333048, or a cytosine at rs1333049. 
     
     
         48 . The method of  claim 43 , wherein the polymorphism comprises at least one of the following positions on human chromosome 9 as defined by NCBI Build 36.1 Coordinates: a guanine at position 22062264; a cytosine at position 22062301; an adenine at position 22062638; a guanine at position 22062719; a thymine at position 22071397; a thymine at position 22071850; a thymine at position 22078090; a guanine at position 22078094; a thymine at position 22078260; a deletion at position 22078465; a guanine at position 22088574; a guanine at position 22088619; an insertion at position 22089755; a cytosine at position 22090176; a cytosine at position 22091702; a thymine at position 22092165; a thymine at position 22093183; a guanine at position 22093341; a guanine at position 22093813; a cytosine at position 22095927; an adenine at position 22096731; a cytosine at position 22100131; an insertion at position 22101587; a cytosine at position 22102241; a guanine at position 22102427; a cytosine at position 22104469; a guanine at position 22104495; a cytosine at position 22105286; a guanine at position 22106046; a cytosine at position 22106220; an insertion at position 22110491; a cytosine at position 22113766; an adenine at position 22114123; a thymine at position 22114140; a cytosine at position 22115347; or a cytosine at position 22115503. 
     
     
         49 . A kit adapted to practice the method of  claim 31  and comprising a probe for said marker. 
     
     
         50 . A kit adapted to practice the method of  claim 37  and comprising a probe for said marker.