SNP Detection for Personalized Beta Blocker Therapy

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Solution Overview

Problem

Postoperative atrial fibrillation (AF) is a common complication following coronary artery bypass grafting surgery, associated with increased healthcare costs and complications, and beta-blockers do not effectively prevent AF in approximately 20% of patients, necessitating a more personalized approach to treatment.

Innovation Solution

Identifying specific single nucleotide polymorphisms (SNPs) such as rs3740563, rs4752292, rs11198893, and rs10787959 in nucleic acid samples from patients undergoing coronary artery bypass grafting surgery to determine the risk of altered effectiveness of beta-blocker therapy, allowing for personalized treatment strategies, including the use of nondihydropyridine calcium channel blockers and amiodarone.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If beta-blockers are administered to prevent postoperative atrial fibrillation, then the incidence of AF is reduced in the majority of patients, but approximately 20% of patients still develop AF despite beta-blocker use

Engineering Contradiction:
Improveeffectiveness of beta-blocker therapyVSAvoidresponse variability to beta-blocker treatment
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention applies parameter changes by identifying genetic polymorphisms (specific alleles at SNPs rs3740563, rs4752292, rs11198893, and rs10787959) that alter the response to beta-blocker therapy. By detecting these genetic parameters, the invention stratifies patients into those who will respond to beta-blockers and those who will not, thereby changing the therapeutic parameter from universal administration to targeted administration based on genetic profile.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If universal beta-blocker therapy is administered to all patients undergoing CABG, then treatment coverage is maximized, but healthcare costs increase due to treating patients who will not respond

Engineering Contradiction:
Improveprevention of postoperative AFVSAvoidhealthcare costs
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The invention applies preliminary action by performing genetic testing for specific SNPs before CABG surgery to identify patients who are likely to develop AF despite beta-blocker therapy. This allows clinicians to pre-select patients who would benefit from alternative prophylactic strategies (such as nondihydropyridine calcium channel blockers or amiodarone) before surgery, avoiding unnecessary beta-blocker administration to non-responders and reducing overall healthcare costs.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If genetic testing for multiple SNPs is performed to identify patients at risk of altered beta-blocker effectiveness, then personalized treatment can be implemented, but the complexity of the diagnostic process increases

Engineering Contradiction:
Improvepersonalized treatment capabilityVSAvoiddiagnostic process complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention applies segmentation by dividing the diagnostic process into discrete, testable components - specifically testing for four distinct single nucleotide polymorphisms (rs3740563, rs4752292, rs11198893, and rs10787959). Each SNP can be tested independently using standard molecular biology techniques, allowing the complex genetic assessment to be broken down into manageable, routine laboratory tests that can be performed sequentially or in parallel.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS10378056B2Compositions and methods for identifying altered effectiveness of beta blocker therapy
Publication Date: 2019.08.13 DUKE UNIV

AI summary

The present invention provides a method of identifying a human subject as having an increased risk of altered effectiveness of beta blocker therapy, comprising detecting in the subject one or more single nucleotide polymorphism associated with increased risk of altered effectiveness of beta blocker therapy.