In an unexpected finding, a defect in a kidney gene—not a heart gene—appears to predispose a person to heart failure. The variant CLCNKA risk allele is a previously overlooked genetic mechanism affecting the cardio-renal axis, according to findings published in The Proceedings of the National Academy of Science (2011;108:2456-2461).

After variations in the HSPB7 gene demonstrated an association with heart failure but did not appear to cause it, researchers sequenced the adjacent CLCNKA gene and found that a single change in the DNA sequence there can lead to an approximately 50% reduction in the chloride channel’s ability to shuttle chloride ions across cell membranes and into the urine. If this process is shown to elevate blood levels of renin, ACE inhibitors and aldosterone blockers may help reduce heart-failure risk in individuals with the CLCNKA gene defect.