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Body mass index higher in certain genetic variations
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CHICAGO—The combination of two obesity-related genetic variations may be associated with an increased body mass index (BMI) among severely obese patients undergoing bariatric weight loss surgery, according to a report in the March issue of Archives of Surgery, one of the JAMA/Archives journals.

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Bariatric surgery is a highly effective treatment for patients with morbid (severe) obesity, or a BMI of 40 or higher, according to background information in the article. “Although the long-term effectiveness of bariatric surgery is not surpassed by any other modality, a subgroup of patients remain resistant to weight loss,” the authors write. “Identification of variables that determine the success of bariatric surgery have shown little consistency, and long-term success may depend on not yet identified factors.”

Xin Chu, Ph.D., and colleagues at the Geisinger Clinic, Danville, Pa., assessed 707 morbidly obese adult patients (average age 45.9, average BMI 51.2) undergoing gastric bypass operations at the facility. Demographic, BMI and laboratory data were obtained from electronic medical records. Blood samples were taken and analyzed for two common single nucleotide polymorphisms (SNPs)—variations that occur when a single building block of DNA is altered—previously found to be associated with obesity.

About 21 percent of the patients had two copies of one obesity-related SNP variant,13 percent had two copies of the other SNP and 3.4 percent had two copies of both. The average BMI among those with two identical copies of either obesity-related SNP were not significantly different from those who did not have two copies. However, those with two copies of both SNPs, or two copies of one and one copy of the other, had significantly higher BMIs than the other groups. These individuals comprised less than 20 percent of the total group.

The mechanism by which these genes may influence obesity is not yet known, the authors note. “Our results indicate that the two genes may interact, suggesting that the physiological pathways in which each is involved may be linked in some way,” they write.

“Recent data on the long-term effectiveness of bariatric surgery on BMI suggest that, for most patients, BMI will be maintained substantially below preoperative levels, though some patients regain weigh and relapse toward morbid obesity,” the authors conclude. This subgroup may carry genetic susceptibilities to obesity that overcome the effects of bypass surgery. “The identification of such susceptibility genes may therefore be important in identifying patients at high risk for postoperative weight gain. These studies may also represent some of the first specific examples of ‘surgicogenomics,’ paralleling the well-developed field of pharmacogenomics,” or using genetic information to predict individuals’ responses to medications.
(Arch Surg. 2008;143[3]:235-240.

Editor's Note: This study was supported by the Geisinger Clinical Research Fund. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at} .

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