Genetic test for determining susceptibility for eosinophilic esophagitis

Inventors

Rothenberg, Marc E.Kottyan, LeahHarley, John

Assignees

Cincinnati Childrens Hospital Medical CenterUS Department of Veterans Affairs

Publication Number

US-10294517-B2

Publication Date

2019-05-21

Expiration Date

2035-03-16

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Abstract

Methods and compositions disclosed herein generally relate to determination of susceptibility to eosinophilic esophagitis, asthma, and/or allergic diseases, disorders, and/or pulmonary and/or upper gastrointestinal conditions arising therefrom and/or related thereto and the diagnosis, treatment, and/or management of eosinophilic esophagitis, asthma, and/or allergic diseases, disorders, and/or pulmonary and/or upper gastrointestinal conditions arising therefrom and/or related thereto. Embodiments of the invention relate to the association between genes and specific polymorphisms of genes with eosinophilic esophagitis. Embodiments of the invention can be used to determine and manage patient risk factors for development of eosinophilic esophagitis; this determination can then be used to diagnose eosinophilic esophagitis and to treat a patient diagnosed with eosinophilic esophagitis.

Core Innovation

The invention relates to methods and compositions for determining susceptibility to eosinophilic esophagitis (EoE), asthma, and related allergic diseases and disorders, and for the diagnosis, treatment, and management of these conditions. It discloses the association between certain genes and specific polymorphisms with EoE, enabling the determination and management of patient risk factors for developing EoE, and subsequent use in diagnosis and treatment.

EoE is a chronic, food antigen-driven inflammatory disease of the esophagus characterized by esophageal eosinophil accumulation, fibrosis, stricture formation, and impaired motility. The problem addressed by the invention is the need for improved methods to identify patients at risk or having EoE, as EoE shares genetic overlaps with other allergic diseases but manifests tissue-specifically in the esophagus. Prior to this invention, understanding of genetic susceptibility and correlation with clinical risk was limited.

The invention solves this problem by providing methods to identify patients as having or at risk of developing EoE through genotyping specific genetic variants (rs77569859 in CAPN14, rs2898261 in XKR6, and rs8041227 at 15q13). Based on these genotypes, patients are classified into risk groups (low, moderate, high), enabling targeted diagnosis, such as referral for confirmatory endoscopy, and guiding treatment decisions. Incorporation of additional patient-specific data including non-genetic factors further refines risk classification.

Claims Coverage

The patent includes one independent claim that focuses on a method for diagnosing and treating eosinophilic esophagitis by genotyping specific genetic variants and assigning risk groups.

Genotyping specific genetic variants for EoE risk assessment

Obtaining or receiving a biological sample from the patient and detecting the presence of one or more genetic variants selected from rs77569859 (CAPN14), rs2898261 (XKR6), and rs8041227 (at 15q13 between LOC283710 and KLF13).

Assigning risk groups based on genotype

Assigning the patient into a risk group selected from low, moderate, and high according to specific genotype-risk mappings: rs77569859 (GG high, GA moderate, AA low), rs2898261 (CC high, AC moderate, CC low), and rs8041227 (GG high, AG moderate, AA low).

Diagnosing and treating EoE based on risk group

Diagnosing patients assigned to high or moderate risk groups with EoE and administering EoE therapy to diagnosed patients.

Methods for determining genotype

Determining the presence of genetic variants by extracting DNA from the biological sample and analyzing the DNA using PCR-based genotyping platforms, including 5' nuclease assays, or receiving genotype directly from genotyping equipment.

Therapeutic methods

Administering therapies selected from steroids, proton pump inhibitors, topical glucocorticoids, and inhibitors of eosinophil recruitment, survival, or activation.

The claims cover a method integrating genetic variant detection, risk classification according to defined genotype-risk relationships, diagnosis of eosinophilic esophagitis based on these risk groups, and administration of appropriate therapies, using specific genotyping techniques and sample types.

Stated Advantages

Enables identification and management of patients at risk of developing eosinophilic esophagitis, allowing earlier and targeted diagnosis and treatment.

Facilitates non-invasive genetic testing to stratify patients by risk, reducing unnecessary invasive procedures for low-risk individuals.

Links genetic susceptibility with disease-specific molecular pathways, improving understanding of EoE pathophysiology.

Allows use of computer-implemented systems for efficient risk assignment and clinical decision support.

Documented Applications

Determination of susceptibility to eosinophilic esophagitis in patients via genetic testing.

Diagnosis of eosinophilic esophagitis by assigning patients into risk groups based on genotype analyses.

Guidance for clinical management, including referral for confirmatory diagnostics such as endoscopy, based on genetic risk classification.

Treatment of diagnosed EoE patients with therapies including steroids, proton pump inhibitors, topical glucocorticoids, and inhibitors of eosinophil recruitment, survival, or activation.

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