Gene Polymorphisms Associated with Increased Risk of Hyponatremia
OHSU # 1035
This technology provides methods of diagnosing an increased risk for hyponatremia by assessing the presence of at least one hypofunctioning allele of TRPV4. Abundant evidence suggests that the transient receptor potential channel TRPV4 comprises an element of the central sensor of low osmolality. A large cohort of patients have been genotyped for the polymorphic allele and its presence is over-represented in those subjects with the lowest serum sodium concentrations and who are the greatest risk of developing hyponatremia. This diagnostic can identify a subset of individuals who may be at increased risk for dangerous aberration in water metabolism, both in the unprovoked state and in response to clinical and environmental maneuvers known to result in abnormal water balance. To date, no human mutation in an osmosensing TRP channel has been shown to impact osmoregulation, and no polymorphisms impacting systemic water balance have been reported for any gene.
Aberrant water balance is associated with neurological dysfunction and death. Subtle changes in systemic osmolality cause reversible defects in coordination and cognition. Water excess relative to total body sodium content results in hyponatremia – the most prevalent electrolyte abnormality in hospitalized patients. The elderly are predisposed to water retention. Water retention can cause abnormal thinking and behavior, seizures, coma and death. In patients lacking obvious medical conditions known to predispose to abnormal water retention (e.g., heart, kidney or liver failure), there is no known way to reliably identify which individuals are at increased risk for this potentially life-threatening complication.
Hyponatremia is most common in the elderly population. It is estimated that nearly 7 percent of elderly persons experience some form of hyponatremia. Over the next 20 years, the elderly population in the U.S. will grow faster than the total population when nearly one in five U.S. residents is expected to be 65 years or older. By 2030, the number of people over 65 in the U.S. is estimated to be over 72 million. As the number of elderly individuals increase, so will the cases of hyponatremia.
Hyponatremia is estimated to affect 1-4% of hospitalized patients in the U.S. each year.
In a report from 2005, researchers found hyponatremia in as many as 13% of the runners in the Boston Marathon with life-threatenting hypnatremia in 0.6% of the runners. Several deaths of long-distance runners have been linked to hyponatremia.
Hyponatremia has also been shown to be caused by the administration of numerous drugs, many of these being diuretic agents and medications to treat hypertension and mental health disorders.
David Cohen received his B.S. from Pennsylvania State University and his M.D. from Jefferson Medical College of Thomas Jefferson University. He conducted research and clinical fellowships at Brigham and Women’s Hospital and Harvard Medical School followed by joining OHSU’s Nephrology staff in 1995. Dr. Cohen is currently the Chief of Nephrology at the VA Medical Center in Portland, Oregon and Professor of Medicine at OHSU in the Division of Nephrology & Hypertension.
OHSU 1035 is available for exclusive or non-exclusive licensing.
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