Compositions and Methods for Detecting Predisposition to Cardiovascular Disease DNA Methylation and SNP Signatures for Cardiovascular Risk Screening

This patent describes a kit and methods for assessing a person’s risk of developing cardiovascular disease by combining DNA methylation measurements at specific CpG sites with the genotype of nearby single-nucleotide polymorphisms. The combined epigenetic and genetic signal is intended to give a more reliable prediction than methylation alone, which has worked well for related conditions such as smoking exposure but has had limited power when applied directly to heart disease.

The Problem

Cardiovascular disease covers coronary heart disease, congestive heart failure and stroke, and is the leading cause of death in the United States and a major contributor in Australia. Treatments to reduce morbidity and mortality exist, but their effectiveness depends on identifying at-risk patients early. Conventional screening relies on lipid panels, blood pressure, family history and lifestyle factors. Researchers have shown that DNA methylation patterns can infer the presence of related conditions such as smoking, yet when the same epigenetic methods are applied directly to cardiovascular disease their predictive power drops. One proposed reason is that gene-by-methylation interaction effects obscure the underlying CVD signature. A reliable laboratory test that combines both layers of biological information would help clinicians make better treatment decisions.

What This Invention Does

The patent provides a kit and the associated assay procedures for determining the methylation status of one or more CpG dinucleotides together with the genotype of one or more relevant SNPs. The kit includes nucleic acid primers complementary to bisulfite-converted DNA sequences containing the CpG sites of interest, and separate primers covering the candidate SNP loci. A test sample is processed through bisulfite conversion, the primers detect methylated versus unmethylated CpG dinucleotides, and additional primers distinguish the SNP alleles. The combined output is used to classify the subject’s predisposition to cardiovascular disease and to inform clinical management.

The disclosure extends to methods of identifying subjects at elevated risk and to compositions of primers and probes that target the CpG and SNP positions identified through the inventors’ research.

Key Features

• Combined epigenetic and genetic signal. Uses both DNA methylation and SNP genotype rather than methylation alone, which improves discrimination for CVD where gene-by-methylation interactions otherwise blur the signature.
• Bisulfite-conversion primer chemistry. Standard, widely available laboratory chemistry that can be deployed in clinical and research labs without exotic instrumentation.
• Configurable CpG and SNP panels. The kit covers multiple CpG sites and SNP loci identified by the inventors as informative for CVD risk, supporting flexible panel design.
• Built on prior epigenetic work. Extends the same epigenetic measurement framework that has been shown to reliably detect smoking and related exposures, while adapting it to a harder target.
• Federally supported research base. The work was funded under NIH grants R01DA037648 and R44DA041014, giving the underlying datasets and validation a credible academic basis.

Who Is Behind It

The applicant is the University of Iowa Research Foundation, which manages technology transfer for the University of Iowa. The named inventors are Robert Philibert, a long-standing psychiatry and behavioural genetics researcher whose laboratory has produced widely cited work on DNA methylation as a biomarker for smoking and substance use, and Meeshanthini Dogan, a co-author on much of his epigenetic biomarker work. The Australian application is a divisional of AU 2023254965. The Australian patent attorney of record is Pizzeys Patent and Trade Mark Attorneys in Brisbane.

Why It Matters

Cardiovascular disease prevention is one of the largest opportunities in precision medicine. A practical blood-based screening test that combines methylation and SNP data could give general practitioners and cardiologists a more reliable way to triage patients into intensive prevention pathways, with potential downstream impact on prescribing, lifestyle intervention and insurance underwriting. Australia is a significant market for cardiovascular diagnostics, and locking in protection here positions the Iowa team’s IP for licensing to local pathology providers and reagent suppliers. Divisional filings such as this one often reflect a strategy of preserving claim scope across the patent family while the parent moves through examination.

Related Concepts

• DNA methylation – the epigenetic modification at the heart of this assay.
• Epigenome-wide association study – the broader research methodology used to find informative CpG sites.
• Polygenic score – the SNP-based equivalent in modern cardiovascular risk prediction.
• Bisulfite sequencing – the conversion chemistry that lets the assay distinguish methylated cytosines.
• Framingham Risk Score – the long-standing clinical benchmark that any new CVD risk tool is compared against.

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AU 2026201866 was published in the Australian Official Journal of Patents on 2 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.