KCNJ11 E23K polymorphism increases susceptibility for cardiovascular mortality in patients with type 2 diabetes

Date: Sep-27-2013An analysis of genetic variations known to be associated with type 2 diabetes has shown that the 'bad' variant of one, the KCNJ11 E23Kpolymorphism, also increases the risk of cardiovascular mortality by at least 20%. Some 40% of the type 2 diabetic population has this bad variant. The research is by Associate Professor Valeriya Lyssenko, Lund University, Malmö, Sweden, and Steno Diabetes Center, Gentofte, Denmark, and Dr Sami Alkayyali, Lund University, Malmö, Sweden. The research is presented at the annual meeting of the European Association for the Study of Diabetes (EASD), in Barcelona, Spain.

While genome-wide association studies have identified some 60 variants or 'polymorphisms' associated with type 2 diabetes, their total effect on total mortality or cardiovascular (CVD) mortality has not yet been studied. This new research explored whether these variants were also associated with total or CVD-mortality in patients with type 2 diabetes.

The study analysed 30-36 common genetic variants in total of 3,610 patients from the local Malmö Scania Diabetes Registry (SDR), the Malmö Diet and Cancer Study (MDCS) and the Diabetes Alliance for Research in England (DARE) cohorts. Replication of KCNJ11 rs5219 (E23K) for association with total and CVD mortality was performed in the Botnia, the Diabetes Genetics Initiative (DGI) and the Steno studies.

In the combined analyses of the SDR, MDCS and DARE cohorts, carriers of the 'bad' variant of KCNJ11 E23k had increased total mortality rates (42.0% vs 39.5%; with analysis showing a 10% increased risk of overall mortality) and particularly increased cardiovascular disease-related mortality (44.5%vs 39.5%, with analysis showing a 26% increased risk).

A second meta-analyses of the studies above and the Diabetes genetics initiative (DGI) and the Botnia studies included 5,469 patients with type 2 diabetes, 820 of whom had CVD-related deaths. In this analysis, carriers of 'bad' variant had a 21% increased risk fold increased risk for CVD-mortality.

Dr Alkayyali says: "We demonstrated that the KCNJ11 E23K variant is associated with increased risk of CVD-mortality in patients with type 2 diabetes, and, thus, seems to be a common denominator in the pathogenesis of type 2 diabetes and cardiovascular complications."

He adds: "Researchers have seen an increased risk for mortality in patients with diabetes who are treated with sulfonylureas. KCNJ11 gene encodes for the receptor to the sulfonylureas. It is therefore important to determine if mortality risk is different in patients with risk and non-risk KCNJ11 E23K variant."

He concludes: "We want to collaborate with more researchers around these observations, aiming to identify patients treated with sulfonylureaswho may be at different risks for mortality depending on their genetic background."
Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.