But the mutations in the melanocortin 4 receptor (MC4R) gene are rare. Although there are up to 34 mutations, only 2% to 3% of very obese people carry them.

German researchers compared the body weights of 181 relatives from 25 families of extremely obese people carrying the MC4R mutations.

Carriers of the relevant mutations had a significantly higher body mass index (BMI), which is the formula used to calculate appropriate weight for height, than those who did not.

BMI is calculated by dividing weight by height squared and multiplying by 703 (imperial measures) or 10,000 (metric measures). A BMI of 30 indicates clinical obesity.

The impact of the genetic mutations was twice as great for women as for men. In women the mutations accounted for 9.5 kg/ metre2 height in middle aged women and for 4 kg in middle aged men.

While rates of obesity dropped substantially between first and second degree relatives of obese patients without the gene mutations, this was far less obvious among relatives of those who were carriers. This further emphasises the impact of the mutations, say the authors.

"MC4R mutations entail a strong predisposition to obesity," conclude the authors. But they add that the high rate of body fat among the relatives of the carriers suggests that the mutations do not, by themselves, account for obesity.

Other genetic and environmental factors play their part, they say, perhaps illustrated by the fact that thin people can also carry the genetic mutations.

bma

A measure of body weight relative to height. BMI can be used to determine if people are at a healthy weight, overweight, or obese. To figure out BMI, use the following formula:

A body mass index (BMI) of 18.5 up to 25 refers to a healthy weight, a BMI of 25 up to 30 refers to overweight and a BMI of 30 or higher refers to obese.

The PTC cells showed over-expression of genes known as CITED1, claudin-10 (CLDN10), and insulin-like growth factor binding protein 6 (IGFBP6). It also showed no change in two genes, caveolin-1 (CAV-1) or caveolin-2 (CAV-2). FTC cells, on the other hand, showed no expression by CLDN10 and low activity by IGFBP6 and/or by CAV1 and CAV2.

If verified in a larger number of tumors, these genes, in combination with other known genetic changes in thyroid cancer cells, form the basis for a valuable diagnostic tool, says Eng, a recipient of the Doris Duke Distinguished Clinical Scientist Award.

Our work begins to elucidate the fundamental differences and similarities between these two types of thyroid cancer, which should help in the future to develop new therapies, Eng says.

Clinical testing for the genetic differences can be done using polymerase chain reaction (PCR) technology, which is far more available and far less costly than microarray analysis.

Other Ohio State researchers involved in the study were first author Micheala A. Aldred, Sandya Liyanarachchi, Natalia S. Pellegata, Sissy Jhiang, Ramana V. Davuluri and Albert de la Chapelle.

Funding from the National Cancer Institute, and a gift from the Brown family, in memory of Welton D. Brown, supported this research.

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