US2008274471A1PendingUtilityA1

Methods for detecting an increased risk for coronary heart disease

Individually held — no corporate assignee on recordPriority: May 2, 2007Filed: May 2, 2008Published: Nov 6, 2008
Est. expiryMay 2, 2027(~0.7 yrs left)· nominal 20-yr term from priority
C12Q 2600/156C12Q 1/6883C12Q 2600/172C12Q 2600/106
67
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Claims

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.

Claims

exact text as granted — not AI-modified
1 . A method for determining whether a human subject carries an allele associated with an increased risk for coronary heart disease, comprising detecting in vitro whether the human subject has an RA-CHR9 allele. 
     
     
         2 . A method for identifying a human subject at increased risk for coronary heart disease, comprising using an in vitro assay to detect the presence of a risk allele in a region extending from 22,062,301 to 22,120,389 of human chromosome 9 in a human subject that is more frequently present in a population of humans with coronary heart disease than in a population of humans that do not have coronary heart disease, wherein the presence of the risk allele indicates that the human subject has an increased risk for coronary heart disease. 
     
     
         3 . A method for identifying a human subject at increased risk for coronary heart disease, comprising using an in vitro assay to detect the presence of a polymorphism with a linkage disequilibrium of at least r 2 =0.89 with a risk allele in a region extending from 22,062,301 to 22,120,389 of human chromosome 9 in a human subject, wherein the presence of the polymorphism indicates that the human subject has an increased risk for coronary heart disease. 
     
     
         4 . The method of  claim 1  or  2 , wherein the allele is detected using mass spectroscopy, oligonucleotide microarray analysis, allele-specific hybridization, allele-specific PCR or sequencing. 
     
     
         5 . The method of  claim 1 , wherein detecting the RA-CHR9 allele comprises detecting a single nucleotide polymorphism (SNP). 
     
     
         6 . The method of  claim 5 , wherein the SNP on human chromosome 9 is at least one of the following positions as defined by NCBI Build 36 Coordinates: 22062301; 22062638; 22067543; 22062719; 22071397; 22071850; 22078090; 22078094; 22078260; 22086055; 22088574; 22088619; 22090176; 22091702; 22092165; 22093183; 22093341; 22093813; 22095927; 22096731; 22100131; 22102241; 22102427; 22104469; 22104495; 22105026; 22105286; 22106046; 22106220; 22113766; 22114123; 22114140; 22115347; or 22115503. 
     
     
         7 . The method of  claim 5 , wherein the SNP is at rs9632884, rs6475606, rs10757272, rs10757274, rs4977574, rs2891168, rs1333042, rs2383206, rs1333048, or rs1333049. 
     
     
         8 . The method of  claim 5 , wherein the SNP is at rs10757274 or rs2383206. 
     
     
         9 . The method of  claim 1 , wherein detecting the RA-CHR9 allele comprises detecting a deletion or insertion. 
     
     
         10 . The method of  claim 9 , wherein the deletion or insertion is at one of the following positions on human chromosome 9: 22078465, 22089755, 22101587, or 22110491. 
     
     
         11 . A method for determining whether a human subject is at increased risk for coronary heart disease, comprising using an in vitro assay to detect the presence of a human chromosome 9 haplotype comprising a guanine nucleotide at rs10757274 or a guanine nucleotide at rs2383206 in a human subject, wherein the presence of the haplotype indicates that the human subject has an increased risk for coronary heart disease. 
     
     
         12 . The method of  claim 11 , wherein the haplotype comprises a guanine nucleotide at rs10757274 and a guanine nucleotide at rs2383206. 
     
     
         13 . The method of  claim 11  or  12 , wherein the haplotype 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. 
     
     
         14 . The method of  claim 11  or  12 , wherein the haplotype comprises at least one of the following positions on human chromosome 9: 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. 
     
     
         15 . The method of  claim 2 , wherein the risk allele is at one of the following positions on human chromosome 9: 22062301; 22062638; 22062719; 22067543; 22071397; 22071850; 22078090; 22078094; 22078260; 22078465; 22086055; 22088574; 22088619; 22089755; 22090176; 22091702; 22092165; 22093183; 22093341; 22093813; 22095927; 22096731; 22100131; 22101587; 22102241; 22102427; 22104469; 22104495; 22105026; 22105286; 22106046; 22106220; 22110491; 22113766; 22114123; 22114140; 22115347; or 22115503. 
     
     
         16 . The method of  claim 2 , wherein the risk allele is at rs9632884, rs6475606, rs10757272, rs10757274, rs4977574, rs2891168, rs1333042, rs2383206, rs1333048, or rs1333049. 
     
     
         17 . The method of  claim 2 , wherein the risk allele is at rs10757274 or rs2383206. 
     
     
         18 . The method of  claim 11 , wherein the haplotype is in a region extending from 22,062,301 to 22,120,389 on human chromosome 9. 
     
     
         19 . The method of  claim 1 ,  2 ,  3  or  11 , wherein the human subject is not an African American. 
     
     
         20 . The method of  claim 1 , wherein the human subject is heterozygous for the RA-CHR9 allele. 
     
     
         21 . The method of  claim 11 , wherein the human subject is heterozygous for the haplotype. 
     
     
         22 . The method of  claim 2 , wherein the human subject is heterozygous for the risk allele. 
     
     
         23 . The method of  claim 3 , wherein the human subject is heterozygous for the polymorphism. 
     
     
         24 . The method of  claim 1 , wherein the human subject is homozygous for the RA-CHR9 allele. 
     
     
         25 . The method of  claim 11 , wherein the human subject is homozygous for the haplotype. 
     
     
         26 . The method of  claim 2 , wherein the human subject is homozygous for the risk allele. 
     
     
         27 . The method of  claim 3 , wherein the human subject is homozygous for the polymorphism. 
     
     
         28 . A method for identifying a human subject at increased risk for coronary heart disease, comprising using an in vitro assay to detect the presence of a SNP at rs1333049, wherein the presence of a SNP at rs1333049 indicates that the human subject has an increased risk for coronary heart disease. 
     
     
         29 . The method of  claim 28 , wherein the SNP is a cytosine nucleotide at rs1333049. 
     
     
         30 . A kit comprising one or more components for detecting the presence of an RA-CHR9 allele in a human subject.

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