Approved Research

Interaction between a common variant in the ketohexokinase gene and fructose intake on cardiometabolic outcomes

Lay summary

The high frequency of type 2 diabetes, hypertension and coronary artery disease in Western society has been attributed to, amongst others, the rapid rise in fructose consumption. Fructose is not only present in fruit and vegetables, but also in many processed foods.

New drugs have been developed that impair the processing of fructose in the human body. This drug inhibits a specific protein, called ketohexokinase. It is expected that this drug can be used to treat type 2 diabetes and hypertension, and to prevent coronary artery disease. It will, however, take years before we know that for sure.

All humans carry small variations in their DNA, also in the DNA that encodes the ketohexokinase protein. By studying these DNA variations, we can get a glimpse of what the effects of ketohexokinase inhibition will be. We expect that these effects will be the greatest in humans consuming large amounts of fructose.

We, therefore, will study the effects of fructose consumption on blood pressure, blood sugar and lipid levels in the UK Biobank. In addition, we will study whether these effects differ between individuals who carry different DNA variants encoding ketohexokinase.

It is expected that this project, which will take one year, will provide more information on the effects of a new drug (ketohexokinase inhibition) on type 2 diabetes and blood pressure.

Scope extension:

Is there an interaction between a common variant in the ketohexokinase gene (rs2304681) and fructose intake on cardiometabolic outcomes?

Aim: to study the interaction between fructose intake and rs2304681 on:

- serum triglycerides

- serum SHBG

- systolic and diastolic blood pressure

- serum glucose and HbA1c

Since daily average fructose/sucrose intake data has just been returned to the UK biobank we wish to use these variables the study the same research aim (rather than calculating fructose intake ourselves).