Obesity Gene Variants Described by New Genomic Technique

DNA variants in two nervous system genes that are associated with an excessively high BMI have been identified in a new study.

Kelly Frazer and colleagues from UC San Diego, Scripps Translational Science Institute and Sanofi-Aventis used the resequencing of a candidate area of the genome in a large number of individuals followed by screening for genetic markers within this region that are associated with the disease or condition in question.

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"We sequenced two intervals encoding the enzymes FAAH and MGLL which modulate the levels of endocannabinoids present in the brain and peripheral tissues that are involved in the regulation of energy balance and appetite," said Frazer.

"The level of these endocannabinoids is high in obese patients, and thus these two enzymes provide strong candidates to examine for a genetic association with BMI," he said.

In these two genes, the researchers were able to identify four regions associated with BMI: the FAAH promoter, MGLL promoter, MGLL intron 2, and an enhancer in the MGLL intron 3.

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Further testing of one of these regions revealed rare variants that were associated with increased levels of endocannabinoids in the plasma, which is consistent with previous findings.

The study was published in BioMed Central's open access journal Genome Biology.

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