Methods of treating liver diseases with phosphodiesterase 3B (PDE3B) inhibitors

A method of treating a human subject with a therapeutic agent that treats or inhibits a liver disease or type 2 diabetes, wherein the subject is suffering from a liver disease or type 2 diabetes, the method comprising the steps of:

• determining whether the subject has a Phosphodiesterase 3B (PDE3B) predicted loss-of-function or missense variant nucleic acid molecule encoding a human PDE3B polypeptide by:
• obtaining or having obtained a biological sample from the subject;
• and
• performing or having performed a sequence analysis on the biological sample to determine if the subject has a genotype comprising the PDE3B predicted loss-of-function or missense variant nucleic acid molecule;
• and
• when the subject is PDE3B reference, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits the liver disease or type 2 diabetes in an amount that is greater than a standard dosage amount, and administering to the subject a PDE3B inhibitor;
• and
• when the subject is heterozygous for a PDE3B predicted loss-of-function or missense variant nucleic acid molecule, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits the liver disease or type 2 diabetes in an amount that is the same as or less than a standard dosage amount, and administering to the subject a PDE3B inhibitor;
• when the subject is homozygous for a PDE3B predicted loss-of-function or missense variant nucleic acid molecule, then administering or continuing to administer to the subject the therapeutic agent that treats or inhibits the liver disease or type 2 diabetes in an amount that is the same as or less than a standard dosage amount;
• wherein the presence of a genotype having the PDE3B predicted loss-of-function or missense variant nucleic acid molecule encoding the human PDE3B polypeptide indicates the subject has a decreased risk of developing the liver disease or type 2 diabetes;
• and
• wherein the PDE3B inhibitor comprises an antisense nucleic acid molecule, a small interfering RNA (siRNA), or a short hairpin RNA (shRNA) that hybridizes to a PDE3B mRNA.