Association With Body Mass Index In Young Women, Psychiatric Symptoms, And Interaction With The Dopamine d2 Receptor (DRD2) Gene.

September 15, 1996

Genetic Variants of the Human Obesity Gene
Contact: Rachel Lisman,

This article will be published in the September issue of Molecular Psychiatry, a peer-reviewed journal published by Stockton Press/Macmillan Press.

EMBARGOED UNTIL SEPTEMBER 15, 1996 -- In a study reported in the current issue of the journal Molecular Psychiatry, researchers at City of Hope National Medical Center, Duarte, California, USA and Loma Linda University, Loma Linda, California, USA examined a complex, genetically variable region (polymorphism) close to the human obesity (OB) gene and found that certain genetic variants next to the human OB gene are associated with obesity in young women, but not young men. They also found that the genetic variants at the OB gene were also associated in these women with depression and anxiety, two of the behaviors most often associated with obesity. The results suggest the depression was a direct result of the OB gene variants and not just secondary to the obesity.

The cloning and sequencing of the mouse and the human obesity (OB) genes have been greeted with enormous excitement. When mice have a defective OB gene on both chromosomes, they are very obese and treatment with leptin, the product of the OB gene, causes rapid weight loss. This led to the hope that obese humans also had a defective OB gene, and treatment with leptin would also cause weight loss. However, many subsequent studies have shown that obese humans have too much leptin, not too little, and no mutations of the OB gene itself were found. Thus, the OB gene - leptin story is far more complex than originally thought.

In 1993 DE Comings and colleagues found that variants of the dopamine D2 receptor gene (DRD2), originally reported by K Blum and EP Noble as being associated with severe alcoholism, were also associated with obesity. Blum and Noble confirmed this association, and both groups found an association between the DRD2 gene and drug addiction. All three of these substances (alcohol, drugs and food), stimulate the reward pathways of the brain. Now Comings and coworkers found that the OB and DRD2 genes were additive in their effect on obesity in young women. Both genes combined accounted for 22% of the obesity in young women.

These results are consistent with obesity being the result of many different genes (polygenic), with a greater involvement of genetic factors in women and younger subjects, and suggest that variants of the OB gene are causally involved not only with human obesity but with its associated behavioral disorders. An independent commentary by Dr. Gerald J. LaHoste (University of California at Irvine, USA; FAX: + 1 714 824-2447; phone: +1 714 824-4722; e-mail: also appears in the current issue of Molecular Psychiatry.

Authors: DE Comings, R Gade, J MacMurray, D Muhleman, P Johnson, R Verde, WR Peters. City of Hope National Medical Center, Duarte, California, USA and Loma Linda University, Loma Linda, California, USA Molecular Psychiatry 1996; vol. 1, issue 4 (September 1996).
***For information on the scientific aspects of the article please contact the author: Dr. David E. Comings, Department of Medical Genetics,
City of Hope National Medical Center,
1500 East Duarte Road, Duarte, CA 91010-0269, USA
phone: +1 (818) 359-8111; FAX: +1 (818) 301-8980

Editor: Julio Licinio, MD
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