POLYNUCLEOTIDES AND POLYPEPTIDES LINKED TO BLOOD PRESSURE REGULATION AND/OR FATIGUE

摘要

The present invention relates to genetic mutations in the corticosteroid binding globulin (CBG) gene or to aberrant CBG expression products, which segregate with at least one condition selected from hypotension or a fatigue related disorder. The invention also relates to methods for detecting such mutations or expression products, as a diagnostic for said at least one condition, either before or after the onset of clinical symptoms. More specifically, the present invention provides a method for detecting the presence or diagnosing the risk of at least one condition selected from hypotension or a fatigue related disorder by determining the presence of at least one mutation in the sequence of a CGB gene or of an aberrant CBG expression product, which correlates with the presence or risk of said at least one condition. The present invention also encompasses a method of detecting genetic mutations or aberrant expression products, which cause a predisposition to at least one condition selected from hypotension or a fatigue related disorder, by first determining the sequence of a CGB gene or expression product thereof from subjects known to have said at least one condition and comparing the sequence to that of wild-type CBG genes or wild-type CBG expression products to thereby identify said mutations or aberrant expression products. The invention is also concerned with isolated nucleic acid sequences, which correspond, or which are complementary, to at least a portion of a CBG gene or transcript thereof, wherein the sequences contain a mutation or aberration, which correlates with the presence or risk of said at least one condition. The invention further relates to isolated mutant or aberrant CBG polypeptides encoded by mutant CBG genes or by aberrant transcripts thereof. The invention also relates to use of functional CBG polynucleotides, functional CBG polypeptides and glucocorticoids in methods for treating or preventing one or more of said conditions.