Fat Mass And Obesity-associated Genes Increase Risk Of Disease In Mexican-Americans

"Our results confirm the association between FTO and fat mass and indicate that the 5-LO promoter modifies the association between FTO and lipid levels," says Mary Helen Black, candidate for PhD in Statistical Genetics and Genetic Epidemiology, at the Keck School of Medicine of USC and lead author of the study. "The genetic interaction between 5-LO and FTO was significantly associated with an inverse relationship between triglycerides and HDL levels."

The study examined 1286 participants from 165 Mexican American family members of a proband with a history of gestational diabetes and 107 control trios from the BetaGene study. Results suggest subjects who have the FTO rs9939609 A allele and at least one 5-LO short repeat allele had a 26 percent higher triglyceride count and 8 percent lower HDL cholesterol levels compared to participants with the FTO TT genotype. In contrast, among participants with two 5-LO long repeat alleles, those with an FTO A allele showed very little change in triglycerides or HDL compared to those with the FTO TT genotype.

"Understanding the interaction between these genes may help us understand the mechanism by which FTO affects adiposity. Because obesity and dyslipidemia are often precursors to diabetes, these gene interactions may play a vital role in future drug target development, which is another step toward advancing personalized medicine," Black says.

The findings were presented as an oral presentation on Sunday, June 8, at the American Diabetes Association 68th Scientific Sessions held in San Francisco. Authors of the study "Arachidonate 5-Lipoxygenase (5-LO) Modifies the Association Between Fat Mass- and Obesity-Associated Gene (FTO) and Lipids in Mexican Americans (MA),"  include Mary Helen Black, Jaana Hartiala, Anny H. Xiang, Enrique Trigo, Jean M. Lawrence, Thomas A. Buchanan, Richard M. Watanabe, Hooman Allayee.