FTO Gene Variants Increase Risk for Extreme Obesity, Brazilian Study Suggests

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by Margarida Azevedo |

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cancer risk, genetic obesity

Two variants of the FTO gene are strongly associated with the risk of developing extreme obesity, a recent study conducted among the Brazilian population reports.

The study, “Genetic variants in the fat mass and obesity-associated (FTO) gene confer risk for extreme obesity and modulate adiposity in a Brazilian population,” was published in the journal Genetics and Molecular Biology.

Obesity is a worldwide public health problem, affecting more than 650 million adults across the globe as of 2016. In Brazil, about 20% of the population was classified as obese in 2015.
The condition has no singular cause. In fact, scientists have recognized that the risks for and development of obesity are influenced by both environmental and genetic factors. A prior study found that nearly 300 genes, involved in different biological pathways, have been associated with obesity — including the FTO gene.
The highest levels of messenger RNA (mRNA) produced from the FTO gene are found in the arcuate nucleus, an area of the brain with an important role in the control of food intake. mRNA is generated from DNA and used as a template for making proteins.

Still, the link between mutations in FTO and obesity is not consistent across different ethnic groups.

“The influence of FTO variants on the risk of obesity is consistent in Caucasian studies. However, apparently it is not relevant in African Americans, Chinese Han, and Native Oceanic populations,” the researchers said.

The team focused on two variants of the gene. One, known as FTO rs9939609, had shown conflicting results regarding its connection to obesity in Brazil, while the other — FTO rs17817449 — had not been studied in the country.

The study included 292 individuals, median age 33 years, from Rio de Janeiro. A total of 169 had normal weight (body mass index, or BMI, of 22.8 kg/m2) and 123 had extreme obesity and were candidates for bariatric surgery (BMI of 47.6).

The results showed that the frequency of having one or both both gene copies with rs9939609(A) — meaning the variant containing a nucleotide (the building blocks of DNA) called adenine — was significantly higher in the group with extreme obesity than in the controls. Each gene has two copies, or alleles, one inherited from each parent.

Individuals carrying rs9939609(A) were 1.7 times more likely to develop obesity.

Likewise, the frequency of people carrying two alleles with rs17817449 (TT, meaning the nucleotide called thymine) also was higher in the obese group. Individuals carrying both alleles with this variant had a 4.5 times higher likelihood of developing extreme obesity, while those carrying just one allele with this variant had a 1.98 times higher risk.

The combined effect of having these risk alleles also was examined. The researchers found that individuals in the obesity group had a higher average number of risk alleles (2.05) compared with those with normal weight (1.52). In addition, the risk of being obese increased 1.37-fold for each risk allele an individual had.

Statistical analysis showed that both variants were associated with BMI and body weight, and that rs17817449 was also associated with triglycerides levels in the blood. A high level of triglycerides in the blood can increase the risk of heart disease.

“We identified that FTO rs9939609 and rs17817449 polymorphisms [variants] have a strong association with extreme obesity and adiposity [fat tissue] modulation in a Brazilian population sample,” the scientists said.

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