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A Multilocus Genotyping Assay for Cardiovascular Disease

  • Suzanne Cheng , Céline Pallaud , Michael A. Grow , Stephen J. Scharf , Henry A. Erlich , William Klitz , Clive R. Pullinger , Mary J. Malloy , John P. Kane , Gérard Siest and Sophie Visvikis
Published/Copyright: June 1, 2005
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Volume 36 Issue 8

Abstract

In our efforts to develop diagnostic tests for complex multifactorial disorders, and to assist the research community in evaluating genetic markers for predisposition to cardiovascular disease, we have developed a prototype assay to genotype up to 35 variable sites among 15 genes. The candidate markers in this panel were selected from biological pathways likely to contribute to the development and progression of cardiovascular disease. Each sample is amplified in two multiplex polymerase chain reactions that are then hybridized to an array of immobilized oligonucleotide probes. The assay has been applied to a population-based cohort representing 238 families; allele frequencies observed among 455 unrelated parents from this cohort agree with available literature values. Data from a cohort of 142 lipid-clinic patients were used to explore locus associations with arterial occlusion, as measured by quantitative angiography. This prototype assay provides a research tool for studies to assess the association of multiple markers with disease, and for clinical studies to evaluate marker association with patient responsiveness to experimental therapies.

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Published Online: 2005-06-01
Published in Print: 1998-08-01

Copyright © 1999 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. Human Genomics: The Basis of the Medicine of Tomorrow. Recent Progress in Molecular Biology Technology. First IFCC-Roche Conference – Singapore, 15–18 March 1998
  2. Does Clinical Chemistry Have a Future?
  3. The Human Genome Project: From Mapping to Sequencing
  4. The Human Genome Project and the Role of Genetics in Health Care
  5. Mutation Detection and Mutation Databases
  6. Population Genomics: Laying the Groundwork for Genetic Disease Modeling and Targeting
  7. Oligonucleotide-Based Gene Therapy for Cardiovascular Disease
  8. Signal Transduction Pathways and Modulation of Gene Activity
  9. Do Overexpressed Oncoproteins Cause Malignant Growth of Cancer Cells? – Studied by Antisense Oligonucleotides
  10. Ethical and Legal Issues in the Procurement, Storage and Use of DNA
  11. DNA Extraction and Stability for Epidemiological Studies
  12. Simple and Broadly Applicable Sample Preparation by Use of Magnetic Glass Particles
  13. A Multilocus Genotyping Assay for Cardiovascular Disease
  14. Optimized Non-Radioactive Protein Truncation Test for Mutation Analysis of the Adenomatous Polyposis Coli (APC) Gene
  15. Monitoring of Inhibitors of Enzymatic Amplification in Polymerase Chain Reaction and Evaluation of Efficacy of RNA Extraction for the Detection of Hepatitis C Virus Using the Internal Control
  16. Quantification of Relative Expression of Genes with Homologous Sequences Using Fluorescence-Based Single-Strand Conformation Polymorphism Analysis – Application to Lactate Dehydrogenase and Cyclooxygenase Isozymes
  17. Automation of Polymerase Chain Reaction-Based Systems for Detection of Hepatitis C Virus RNA
  18. A Simple PCR with Different 3′ Ends of the Third Primer for Detection of Defined Point Mutations: HCV Genotyping as an Example
  19. Two Quantitative Methods for Imaging Samples in Molecular Biology
  20. Restriction Digest PCR (RD-PCR) for the Analysis of Gene Mutations. Application to Ki-ras
  21. Direct Detection of Mycobacterium tuberculosis in Respiratory Specimens Using an Automated DNA Amplification Assay and a Single Tube Nested Polymerase Chain Reaction (PCR)
  22. Quantitative Detection of Hepatitis B Virus DNA with a New PCR Assay
  23. Molecular Diagnostics for Cardiovascular Disease
  24. Association of Apolipoprotein E Polymorphism and Concentration with Serum Lipids and Apo-lipoprotein Level in the Chinese fromShanghai
  25. Angiotensin Converting Enzyme Gene Polymorphism in Coronary Artery Disease: The Indian Scenario
  26. Mutation C677T of Methylenetetrahydrofolate Reductase Gene Is Not Associated with Coronary Artery Disease, but Possibly with Albuminuria, in Type 2 Diabetic Patients
  27. Cholesteryl Ester Transfer Protein Mutations, Protein Activity and HDL-Cholesterol Concentration
  28. Molecular Biology of Alcohol Dependence, a Complex Polygenic Disorder
  29. Analysis of Clonality in T-Lymphoproliferative Diseases by Multiplex PCR
  30. The Impact of Molecular Diagnosis on Familial Colorectal Cancer
  31. Screening for Tumour Suppressor p16(CDKN2A) Germline Mutations in Israeli Melanoma Families
  32. CGG Repeat Interruptions in the FMR1 Gene in Patients with Infantile Autism
  33. Detection of CYP2D6*3 and 2D6*4 Allelic Variants by PCR-Restriction Fragment Length Polymorphism
  34. Genetic Basis of Congenital Hypothyroidism: Abnormalities in the TSHβ Gene, the PIT1 Gene, and the NIS Gene
  35. Follitropin (FSH) Deficiency in an Infertile Male due to FSHβ Gene Mutation. A Syndrome of Normal Puberty and Virilization but Under-developed Testicles with Azoospermia, Low FSH but High Lutropin and Normal Serum Testosterone Concentrations
  36. Molecular Analysis and Electromyoneurographic Abnormalities in Croatian Children with Proximal Spinal Muscular Atrophies
https://doi.org/10.1515/CCLM.1998.096

Articles in the same Issue

  1. Human Genomics: The Basis of the Medicine of Tomorrow. Recent Progress in Molecular Biology Technology. First IFCC-Roche Conference – Singapore, 15–18 March 1998
  2. Does Clinical Chemistry Have a Future?
  3. The Human Genome Project: From Mapping to Sequencing
  4. The Human Genome Project and the Role of Genetics in Health Care
  5. Mutation Detection and Mutation Databases
  6. Population Genomics: Laying the Groundwork for Genetic Disease Modeling and Targeting
  7. Oligonucleotide-Based Gene Therapy for Cardiovascular Disease
  8. Signal Transduction Pathways and Modulation of Gene Activity
  9. Do Overexpressed Oncoproteins Cause Malignant Growth of Cancer Cells? – Studied by Antisense Oligonucleotides
  10. Ethical and Legal Issues in the Procurement, Storage and Use of DNA
  11. DNA Extraction and Stability for Epidemiological Studies
  12. Simple and Broadly Applicable Sample Preparation by Use of Magnetic Glass Particles
  13. A Multilocus Genotyping Assay for Cardiovascular Disease
  14. Optimized Non-Radioactive Protein Truncation Test for Mutation Analysis of the Adenomatous Polyposis Coli (APC) Gene
  15. Monitoring of Inhibitors of Enzymatic Amplification in Polymerase Chain Reaction and Evaluation of Efficacy of RNA Extraction for the Detection of Hepatitis C Virus Using the Internal Control
  16. Quantification of Relative Expression of Genes with Homologous Sequences Using Fluorescence-Based Single-Strand Conformation Polymorphism Analysis – Application to Lactate Dehydrogenase and Cyclooxygenase Isozymes
  17. Automation of Polymerase Chain Reaction-Based Systems for Detection of Hepatitis C Virus RNA
  18. A Simple PCR with Different 3′ Ends of the Third Primer for Detection of Defined Point Mutations: HCV Genotyping as an Example
  19. Two Quantitative Methods for Imaging Samples in Molecular Biology
  20. Restriction Digest PCR (RD-PCR) for the Analysis of Gene Mutations. Application to Ki-ras
  21. Direct Detection of Mycobacterium tuberculosis in Respiratory Specimens Using an Automated DNA Amplification Assay and a Single Tube Nested Polymerase Chain Reaction (PCR)
  22. Quantitative Detection of Hepatitis B Virus DNA with a New PCR Assay
  23. Molecular Diagnostics for Cardiovascular Disease
  24. Association of Apolipoprotein E Polymorphism and Concentration with Serum Lipids and Apo-lipoprotein Level in the Chinese fromShanghai
  25. Angiotensin Converting Enzyme Gene Polymorphism in Coronary Artery Disease: The Indian Scenario
  26. Mutation C677T of Methylenetetrahydrofolate Reductase Gene Is Not Associated with Coronary Artery Disease, but Possibly with Albuminuria, in Type 2 Diabetic Patients
  27. Cholesteryl Ester Transfer Protein Mutations, Protein Activity and HDL-Cholesterol Concentration
  28. Molecular Biology of Alcohol Dependence, a Complex Polygenic Disorder
  29. Analysis of Clonality in T-Lymphoproliferative Diseases by Multiplex PCR
  30. The Impact of Molecular Diagnosis on Familial Colorectal Cancer
  31. Screening for Tumour Suppressor p16(CDKN2A) Germline Mutations in Israeli Melanoma Families
  32. CGG Repeat Interruptions in the FMR1 Gene in Patients with Infantile Autism
  33. Detection of CYP2D6*3 and 2D6*4 Allelic Variants by PCR-Restriction Fragment Length Polymorphism
  34. Genetic Basis of Congenital Hypothyroidism: Abnormalities in the TSHβ Gene, the PIT1 Gene, and the NIS Gene
  35. Follitropin (FSH) Deficiency in an Infertile Male due to FSHβ Gene Mutation. A Syndrome of Normal Puberty and Virilization but Under-developed Testicles with Azoospermia, Low FSH but High Lutropin and Normal Serum Testosterone Concentrations
  36. Molecular Analysis and Electromyoneurographic Abnormalities in Croatian Children with Proximal Spinal Muscular Atrophies
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