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GEN News Highlights : Jan 21, 2011

Association between DNA Methylation and Obesity May Explain Related Chronic Diseases

Dysregulation of UBASH3A and TRIM3 genes may be the link to cardiovascular diseases and diabetes seen in obese people.

A team of researchers at the Medical College of Georgia’s Georgia Prevention Institute note a link between the presence of fat and chemical changes in DNA that may help explain the increased risk of chronic diseases in obese individuals. Specifically, they observed higher levels of methylation in a portion of the UBASH3A gene and lower levels in part of the TRIM3 gene.

The paper, “Obesity related methylation changes in DNA of peripheral blood leukocytes,” is published online in BMC Medicine.

In the study the researchers conducted a genome-wide methylation analysis of seven obese cases and seven lean controls aged 14 to 18 years. They performed validation of six CpG sites from six genes in 46 obese cases and 46 lean controls aged 14 to 30 years old.

The team observed that in comparison with the lean controls one CpG site in the UBASH3A gene showed higher methylation levels and one CpG site in the TRIM3 gene showed lower methylation levels in the obese cases in both the initial step as well as during validation. On the basis of those results they concluded that obesity is directly associated with methylation change in blood leukocyte DNA.

The next step will be to clarify whether fat causes the DNA changes or vice versa and confirm that the changes contribute to the immune dysfunction associated with obesity. “You need to know disease pathways to find novel medications,” says Xiaoling Wang, Ph.D., genetic epidemiologist at the Georgia Prevention Institute. “We generally know they have a dysregulation of the immune function, but we didn’t know the specific site.”

Both UBASH3A and TRIM3 genes are known to have roles in regulating the immune system, which is often dysregulated in obese individuals. The dysregulation of the genes can result in a level of chronic inflammation that contributes to diseases such as cardiovascular disease and diabetes. Increased methylation can further impact immune function by affecting gene-expression levels, which effects downstream functions of proteins produced by those genes.