As the prevalence of obesity and related health problems continues to increase worldwide, there is considerable effort being devoted to identify genetic mechanisms that control fat storage. Maria De Luca led a team from the University of Alabama at Birmingham, USA, who identified candidate genes using different strains of Drosophila.

On the basis of the results of these fly experiments, the research team then tested three common variations in the human LAMA5 gene and discovered two gene variants that were associated with body shape, one in women of European American descent and the other affecting women of American African descent. As De Luca reports, "We found one variant to be associated with weight and lean mass in both ethnic groups. This variant was also associated with height, total fat mass and HDL-cholesterol, but only in European American women. A different variant was associated with triglyceride levels and HDL-cholesterol in African American women."

The use of flies in a study of human obesity may seem strange, but according to De Luca "Insects store fat like mammals do, as lipid droplets accumulated in the fat body, the functional equivalent of both mammalian liver and white adipose tissue". She adds that, "Drosophila share many components of fat biosynthesis, degradation and regulation with humans, including many of those implicated in diabetes and obesity".

biomedcentral/bmcgenet

Taking into account its links to increased liking of initial smoking, stronger likelihood of getting addicted to nicotine, and greater probability of developing lung cancer, this genetic variant may well constitute a "triple whammy" for smoking-related disease, he says.

A mechanism for explaining increased disease risk, proposed by one of the cancer genetics researchers, is the possibility that certain chemicals, for instance N-nitrosonornicotine in tobacco smoke, act on nicotine receptors in the lung to produce cancer-causing changes - a process known as tumorigenesis.

The new findings linking first smoking experiences, smoking habits, and genetic variation build on previous research by Ovide Pomerleau and Cynthia Pomerleau, Ph.D., at U-M. In studies conducted over a 10-year span, they documented a link between nicotine-dependent smoking and positive first smoking experiences.

Ovide Pomerleau also credits earlier animal research by his colleagues Allan Collins and Jerry Stitzel at the University of Colorado, for providing the impetus for the idea that initial reactivity to nicotine might set the stage for the development of nicotine dependence - and that nicotine receptor genetic variations underlie this process. Stitzel formerly worked at U-M.

The authors of the new paper are Richard Sherva, John P. Rice, Laura J. Bierut and Rosalind J. Neuman of the Department of Psychiatry at the Washington University School of Medicine; Kirk Wilhelmsen of the Department of Genetics and Neurology at the Carolina Center for Genome Sciences; Ovide Pomerleau, Cynthia S. Pomerleau and Sandy M. Snedecor of the U-M Department of Psychiatry; and Scott A. Chasse of the Department of Biochemistry and Biophysics at the University of North Carolina.

Reference: Addiction, doi:10.1111/j.1360-0443.2008.02279.x). The study was funded by the National Institutes of Health. Ovide Pomerleau and Laura Bierut serve on advisory boards for nicotine treatment pharmaceuticals for Pfizer, Inc. Laura Bierut and John Rice at Washington University hold a patent on the CHRNA5 SNP that has been licensed by Perlegen Sciences.

psych.med.umich/niclab/