Thromboembolic disease markers
Inventors
Salas, Eduardo • Soria, José Manuel • Ogorelkova, Miroslava • Elosua Llanos, Roberto • Vila, Joan • Castillo, Sergio
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9518297-B2
Publication Date
2016-12-13
Expiration Date
Abstract
The invention relates to a method for a more appropriate thromboembolic event risk assessment based on the presence of different genetic variant. The invention also relates to a method for determining the risk of suffering a thromboembolism disease by combining the absence or presence of one or more polymorphic markers in a sample from the subject with conventional risk factors for thromboembolism as well as computer-implemented means for carrying out said method.
Core Innovation
The invention relates to management of thromboembolic disease by identifying genetic variants in a biological sample from a human subject and combining the genetic profile with conventional clinical and sociodemographic risk factors to compute individualized probabilities for thromboembolic events, recurrence, and diagnostic assistance. The genetic profile is based on a genetic risk score (GRS) derived from the presence or absence of a combination of specific single nucleotide polymorphisms (SNPs).
The specified SNP combination includes Serpin A10 (protein Z inhibitor) Arg67Stop (rs2232698), Serpin C1 (antithrombin) Ala384Ser (Cambridge II), factor XII C46T (rs1801020), factor XIII Val34Leu (rs5985), Factor II (prothrombin) G20210A (rs1799963), factor V Leiden Arg506Gln (rs6025), factor V Cambridge Arg306Thr, factor V Hong Kong Arg306Gly, and ABO blood group SNPs rs8176719, rs7853989, rs8176743, and rs8176750. The presence or absence of the polymorphisms is identified by hybridization to specific probes spotted on a microarray.
The document describes a logistic-regression risk model with interaction terms and genetic risk scoring to support thromboembolic risk assessment. It also outlines an allele-specific microarray genotyping approach using HairLoop probes and reports association and reclassification results comparing the genetic profile to Factor V Leiden and prothrombin alone. The stated context includes thromboembolic event conditions such as DVT, PE, myocardial infarction, stroke/TIA, and peripheral arteriopathy.
Claims Coverage
The independent claim includes 1 inventive detection core: detecting the presence or absence of a specific combination of SNPs in a human sample by hybridization to microarray-spotted probes (SEQ ID NO:s 1 to 24). Dependent claims further add subject-characteristic determination, narrow the sample to oral tissue or particular biological fluids, and quantify a prolonged travel threshold.
Microarray hybridization detection of a defined SNP combination
A method detecting the presence or absence of a combination of single nucleotide polymorphisms (SNPs) consisting of Serpin A10 Arg67Stop (rs2232698), Serpin C1 Ala384Ser (Cambridge II), factor XII C46T (rs1801020), factor XIII Val34Leu (rs5985), Factor II G20210A (rs1799963), factor V Leiden Arg506Gln (rs6025), factor V Cambridge Arg306Thr, factor V Hong Kong Arg306Gly, and ABO blood group rs8176719, rs7853989, rs8176743, and rs8176750 in a biological sample isolated from a human subject, wherein the presence or absence is identified by hybridization to specific probes consisting of SEQ ID NO:s: 1 to 24 spotted on a microarray.
Determining subject characteristics from a specified list
The method wherein one or more characteristics of the selected subject are determined from a specified list of demographic, clinical, medical history, and laboratory parameters.
Prolonged travel defined as a quantitative threshold
The method wherein prolonged travel is defined as two hours or longer.
Using an oral tissue sample or a biological fluid sample
The method wherein the biological sample is an oral tissue sample obtained by scraping or washing, or is a biological fluid sample.
Specific biological fluids for sample testing
The method wherein the biological fluid sample is saliva, urine, or blood.
Across the claim set, the coverage centers on microarray hybridization-based detection of a defined SNP combination (SEQ ID NO:s 1 to 24) from a human biological sample, with added refinement by determining subject characteristics, applying a two-hour threshold for prolonged travel, and narrowing sample types to oral tissue (scraping or washing) or to saliva, urine, or blood.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?