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Gallstone Gene Discovered by Research Team

A three fold risk increase by gene variant

A group of research scientist from the University of Bonn along with Romanian colleagues has discovered a gene variant which augments the possibility of developing gallstone considerably (Hepatology No. 46, 11 July 2007, DOI 10.1002/hep.21847). Probably one on ten Europeans has this variant in their genetic disposition. The probability of them developing a gallstone in their life time goes up two to three times higher. The particular gene has the directions for constructing a molecular pump which carries cholesterol from the liver into the bile ducts. It is from this cholesterol that gallstones are produced. This modification of the gene results in the pump working enduringly at high speed. The occurrence of gallstone is quite common. In Germany alone 170,000 gallbladder operations are conducted every year.

Gallstones occur very frequently, affecting 15 to 20 per cent of all Germans, usually without noticeable symptoms. But in around a quarter of cases the stones will announce their presence at some time in the form of a painful colic. In the end they often have to be operated. "Gallstones are among the gastrointestinal problems that incur the highest treatment costs," says Professor Dr. Frank Lammert, the Bonn-based specialist for internal medicine.

Gallstones tend to be found at high levels within certain families. In particular, studies of twins provide evidence of a genetic component that boosts risk levels. "We reckon that environmental influences, like the wrong diet, are 70 to 80 per cent responsible for the disorder," explains Lammert who works in the university hospital's Department I headed by Professor Dr. Tilman Sauerbruch. "The rest is caused by genes."

Professor Lammert – working together with his colleagues Dr. Frank Gruenhage, Maja Walier and Professor Dr. Thomas Wienker as well as scientists at the University Clinic of Cluj-Napoca in Romania – has been s earching for the specific genes involved. And he has succeeded, thanks to a study covering 178 women and men from 84 families. They all suffer from gallstones. In 21.4 per cent of cases the subjects were found to be carrying a particular gene variant. In healthy individuals studied as a control group, this variant also occurred, but only at a frequency of 8.6 per cent.

Cholesterol pump at full speed

"The mutation concerns what is known as the ABCG8-gene," Dr. Gruenhage explains. "It contains the instructions for building a pump responsible for transporting the blood lipid cholesterol from the liver into the bile ducts." Most of the gallstones consist to a high degree of crystallised cholesterol. The medical researcher concludes that, "The genetic alteration probably makes the pump run permanently at high speed."

The researchers now hope that their finding will have positive consequences for prevention and therapy. Professor Lammert thinks that, "It may be possible for certain patients to be helped with drug treatments in future, thus avoiding the need for an operation."

However, the genetic contribution to the common problem of gallstones has not been fully explained by this study: "We believe there are at least three or four other gene variants that increase gallstone risk," says the medical scientist.


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