Biochemical Markers for Disease States and Genes for Identification of Biochemical Defects
The present invention relates to a system utilizing biochemical markers and genetic markers to diagnose, predict, and/or monitor intervention of a number of diseases and conditions that have unresolved oxidative stress as an important component. The present invention relates generally to markers and assays for diagnosing, predicting, and monitoring disease, particularly disease-relevant oxidative stress and lipid metabolites and mediators. The oxidative stress, lipid metabolite and lipid mediator biochemical and genetic markers may be further combined with other disease associated or disease relevant markers in methods and assays for diagnosis, monitoring, and assessment of disease, particularly of complex diseases with multi-component factors. The system, methods and assays are applicable to various diseases, including autism, asthma, and Alzheimer's disease.
1 . A method for diagnosis or monitoring a disease or condition in an individual comprising:
(a) collecting one or more biological sample from said individual, wherein the biological sample(s) contain proteins, lipids and nucleic acids of the individual;
(b) analyzing the proteins and/or lipids from a biological sample to determine selective metabolites and oxidation products of arachidonic acid (AHA), docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA); wherein said analyzing results in a metabolic determination of oxidative stress and lipids; and
(c) analyzing the nucleic acids from a biological sample to determine the genotype and/or expression of genes involved in oxidative stress and/or lipid metabolism;
wherein the existence or severity of a disease or condition is determined.
2 . The method of claim 1 further comprising analyzing the nucleic acids from a biological sample to determine the genotype and/or expression of genes associated with or relevant to a selected disease.
3 . The method of claim 1 or 2 wherein analyzing the nucleic acid utilizes PCR analysis.
4 . The method of claim 1 or 2 wherein analyzing the proteins or lipids utilizes mass spectrometry.
5 . The method of claim 1 , wherein step (b) comprises determining levels of one or more of Resolvins D1-D6, E1 or E2 utilizing chemically synthesized and labeled compounds.
6 . The method of claim 2 , wherein genes associated with a disease selected from autism, asthma, and Alzheimer's disease are analyzed.
7 . The method of claim 2 wherein the disease is autism and the genotype and/or expression of one or more genes set out in Table 4 are determined.
8 . The method of claim 2 wherein the disease is asthma and the genotype and/or expression of one or more genes set out in Table 5 are determined.
9 . The method of claim 2 wherein the disease is Alzheimer's disease and the genotype and/or expression of one or more genes set out in Table 6 are determined.
10 . An assay system for diagnosis or monitoring a disease or condition having unresolved oxidative stress as a component which comprises:
(a) collecting a blood, urine or breath sample for biochemical analysis and isolating nucleic acid from said subject;
(b) analyzing the blood, urine or breath sample to determine selective metabolites and oxidation products of arachidonic acid (AHA), docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA); wherein said analyzing results in a metabolic determination of oxidative stress and lipids; and
(c) analyzing the nucleic acids to determine the genotype and/or expression of genes involved in oxidative stress and/or lipid metabolism;
wherein the existence or severity of a disease or condition is determined.
11 . A method for monitoring therapeutic intervention of a disease or condition having unresolved oxidative stress as a component which comprises:
(a) collecting a blood, urine or breath sample for biochemical analysis and isolating nucleic acid from said subject;
(b) analyzing the blood, urine or breath sample to determine selective metabolites and oxidation products of arachidonic acid (AHA), docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA); wherein said analyzing results in a metabolic determination of oxidative stress and lipids; and
(c) analyzing the nucleic acids to determine the genotype and/or expression of genes involved in oxidative stress and/or lipid metabolism;
wherein the existence or severity of a disease or condition is determined.