Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) biomarkers and uses thereof
Methods, compositions, and kits for determining whether a subject has non-alcoholic fatty liver disease (NAFLD) are provided. Methods, compositions, and kits for determining whether a subject has non-alcoholic steatosis are also provided. Methods, compositions, and kits for determining whether a subject has non-alcoholic steatohepatitis (NASH) are also provided.
1. A method of detecting protein levels of a set of biomarkers in a sample from a subject, comprising:
(a) contacting a sample from a subject with a set of capture reagents, wherein the set of capture reagents comprises at least three capture reagents, wherein each capture reagent specifically binds to a different protein selected from: aminocylase-1 (ACY1), sex hormone binding globulin (SHBG), capthepsin Z (CTSZ), c-met (MET), gelsolin (GSN), lower galectin-3 binding protein (LGALS3BP), tissue-type plasminogen activator (PLAT), neural cell adhesion molecule L-1 like protein (CHL1), antithrombin III (SERPINC1), sialic acid binding Ig like lectin 7 (SIGLEC7), and sialic acid binding Ig like lectin 14 (SIGLEC14), and
(b) detecting the amount of each capture reagent conjugated to the protein to which it specifically binds, thereby detecting protein levels of a set of biomarkers in a sample from a subject.
2. The method of claim 1 , wherein the method comprises determining whether a subject has steatosis.
3. The method of claim 2 , wherein the method comprises detecting at least one, at least two, or three biomarkers selected from ACY, SHBG, and SIGLEC14.
4. The method of claim 1 , wherein the method comprises determining whether a subject has non-alcoholic steatohepatitis (NASH).
5. The method of claim 4 , wherein the method comprises detecting at least one, at least two, at least three, at least four, at least five, at least six, or seven biomarkers selected from ACY, SHBG, CTSZ, MET, GSN, LGALS3BP, and SIGLEC7.
6. The method of claim 1 , wherein the method comprises detecting at least three proteins selected from ACY1, SHBG, CTSZ, MET, GSN, LGALS3BP, CHL1, and SERPINC1.
7. The method of claim 1 , wherein the subject has been diagnosed with obesity, abdominal obesity, metabolic syndrome, cardiovascular disease, and/or diabetes.
8. The method of claim 1 , wherein each capture reagent is an antibody or an aptamer.
9. The method of claim 8 , wherein each capture reagent is an aptamer.
10. The method of claim 9 , wherein at least one aptamer is a slow off-rate aptamer.
11. The method of claim 10 , wherein at least one slow off-rate aptamer comprises at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least 10 nucleotides with modifications.
12. The method of claim 11 , wherein each slow off-rate aptamer binds to its target protein with an off rate (t½) of ≧30 minutes, ≧60 minutes, ≧90 minutes, ≧120 minutes, ≧150 minutes, ≧180 minutes, ≧210 minutes, or ≧240 minutes.
13. The method of claim 1 , wherein the sample is selected from a serum sample and a plasma sample.
14. The method of claim 1 , further comprising administering to and/or prescribing to the subject at least one therapeutic agent selected from pioglitazone, vitamin E, and metformin.
15. The method of claim 1 , wherein each capture reagent is an antibody.
16. The method of claim 1 , wherein each capture reagent is detectably labeled.
17. The method of claim 1 , wherein each capture reagent is detectably labeled with a fluorescent or chemiluminescent label.
18. The method of claim 1 , wherein the set of capture reagents is immobilized on a solid support.
19. The method of claim 1 , wherein the method comprises detecting ACY1, LGALS3BP, and SERPINC1.