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Determination of risk for development of cardiovascular disease by measuring urinary levels of podocin and nephrin messenger RNA

a technology of nephrin messenger and urinary podocin, which is applied in the field of disease, can solve problems such as significant risk increas

Inactive Publication Date: 2021-03-25
AMERICAN UNIVERSITY OF BEIRUT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes a system and method for measuring certain genes to determine a person's risk for cardiovascular disease. The genes measured include nephrin, podocin, synaptopodin, WT-1, UCH-L1, pax-8, RAP1GAP, Rap1a, RAP1b, beta-1 integrin, CD2AP, NEPH-1, ZO-1, alpha-actinin 4, Lmx-1b, Pod-1, podocalyxin, podoendin, FAT, and p-cadherin. The system measures these genes using a DNA microarray, which can provide a more accurate and reliable measure of risk compared to other methods. The technical effect of this patent is a better way to identify people at high risk for cardiovascular disease, which can help with preventive care and treatment.

Problems solved by technology

Even minute increases in measurable albuminuria (e.g. from <1 mcg / min to 1-2 mcg / min) conferred a significant increase in risk.

Method used

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  • Determination of risk for development of cardiovascular disease by measuring urinary levels of podocin and nephrin messenger RNA
  • Determination of risk for development of cardiovascular disease by measuring urinary levels of podocin and nephrin messenger RNA
  • Determination of risk for development of cardiovascular disease by measuring urinary levels of podocin and nephrin messenger RNA

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example 1

[0055]Methods:

[0056]Study design: This is a clinical cohort follow-up study in a retrospective patient series participating in a longitudinal biologic sample repository, with additional biomarker measurements.

[0057]Population: Enrolled patients were either outpatients or in-patients with Type II diabetes mellitus seen for initial presentation and then followed for almost 10 years, as well as twenty healthy controls from whom urine was collected for measurement of biomarkers (see below). Consent was secured from study subjects to use their left over urine samples and to review their medical charts for blood / urine test results and for all relevant clinical diagnoses. This study was approved by institutional research board (IRB).

[0058]106 diagnosed type 2 diabetic patients were identified (age: 25-89 years; men / women: 46 / 60) on whom follow up visits (clinical data and urine samples) were available and complete for seven years since their initial visit, whose urinary albumin excretion r...

##ic example 1

Prophetic Example 1

[0081]The blood or any fluid from a subject may be tested for the mRNA levels of nephrin, podocin, synaptopodin, Wilm's Tumor-1 (WT-1), UCH-L1, pax-8, RAP1GAP, Rap1a, RAP1b, beta-1 integrin,CD2-Associated Protein (CD2AP), NEPH-1, ZO-1, alpha-actinin 4, Lmx-1b, Pod-1, podocalyxin, podoendin, FAT, and p-cadherin. The total pellet RNA is isolated using the manufacturer protocol (RNeasy Mini Kit; Qiagen—Germantown, Md.). Quantitation of the absolute nephrin, podocin, synaptopodin, Wilm's Tumor-1 (WT-1), UCH-L1, pax-8, RAP1GAP, Rap1a, RAP1b, beta-1 integrin,CD2-Associated Protein (CD2AP), NEPH-1, ZO-1, alpha-actinin 4, Lmx-1b, Pod-1, podocalyxin, podoendin, FAT, and p-cadherin, mRNA abundance is performed using the CFX96 Touch™ Real-Time PCR Detection System (Bio-rad, USA) using TaqMan Fast Universal PCR Master Mix, with sample cDNA in a final volume of 25 μl per reaction. TaqMan Probes (Applied Biosystems) used were as follows: human NPHS1 (nephrin gene accession numb...

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Abstract

A method for a determining of risk for development of cardiovascular disease by measuring levels of the at least gene of interest is disclosed. The method may identify subjects with moderate albuminuria and diagnosis or predict cardiovascular disease several years before either of these outcomes is detectable by present methodologies.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation application and claims priority to U.S. patent application Ser. No. 14 / 847,946, filed Sep. 8, 2015, which issued as U.S. Pat. No. 10,801,066 on Oct. 13, 2020 and claims the benefit of priority to U.S. Provisional Application Ser. No. 62 / 046,455, filed Sep. 5, 2014, each herein incorporated by reference in their entireties.BACKGROUND[0002]The invention generally relates to disease, and more specifically to diagnosing disease.[0003]In diabetic and non-diabetic individuals who develop vascular disease, a large body of high-quality evidence has established a direct and continuous relationship between Albumin Excretion Rates (AER) and adverse renal and CV outcomes, establishing AER as an independent predictor of CVD. In fact, it was previously demonstrated, in a large population of initially “normoalbuminuric” diabetics, that any increase in albumin excretion is associated with a continuous nonlinear r...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/6883
CPCC12Q1/6883C12Q2600/158
Inventor BADR, KAMAL F.EID, ASSAAD A.HABIB, ROBERT H.
Owner AMERICAN UNIVERSITY OF BEIRUT
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