Study: Mutations in Two Blood Pressure-related Genes May Increase Risk of Obesity

Study: Mutations in Two Blood Pressure-related Genes May Increase Risk of Obesity
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Mutations in two blood pressure-related genes — angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) — may increase a person’s risk of being overweight or obese, according to a study of Tunisians.

While previous studies in several ethnic populations have reported conflicting results, these findings support the existence of a link between obesity and the renin–angiotensin system (RAS), which includes AGT and ACE. RAS regulates blood pressure and the balance of fluids and salts in the body.

Still, larger studies are needed to confirm these associations, along with functional studies to better understand underlying mechanisms, researchers said.

The study, “Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGT M235T) polymorphisms with the risk of obesity in a Tunisian population,” was published in the Journal of the Renin-Angiotensin-Aldosterone System.

Obesity, one of the major worldwide health problems nowadays, is the result of complex interactions between environmental and genetic factors. Nearly 300 genes, involved in distinct biological pathways, have been associated with obesity.

Several studies have investigated a link between variants in RAS-related genes (including AGT and ACE) and obesity, with inconsistent results. Also, data on the genetic background of obesity in North African populations remains limited.

Now, researchers at University of Monastir set out to evaluate a potential link between variants in AGT and ACE genes and overweight-obesity and body mass index (BMI), a ratio of weight to height, in a Tunisian population.

The study included 561 people seen at the Fattouma Bourguiba University Hospital, in Tunisia.

A total of 259 patients with a mean age of 48.9 were overweight or obese (BMI of 25 kg/m2 or higher), while 302 age-matched individuals had normal weight.

Overweight-obese participants had significant prevalence of hypertension, diabetes and altered lipid (fat) levels in the blood, called dyslipidemia, while normal-weight individuals, used as controls, had no such complications.

People with excess weight had higher total levels of cholesterol, as well as increased amounts of high-density lipoprotein (HDL, the so-called “good” cholesterol), and low-density lipoprotein —  LDL, or “bad” cholesterol.

The team analyzed the most studied genetic variants of AGT — M235T, in which a person can have a methionine (M) replaced by a threonine (T) in the resulting protein — and of ACE, in which one can have a deletion (D) or an insertion (I) of a DNA portion. Notably, threonine and methionine are amino acids, the building blocks of proteins.

Since each person inherits two copies of a gene, one from each biological parent, there are three possible combinations for AGT (the “TT,” “MT,” and “MM”), and for ACE (the “DD,” “DI,” and “II” forms).

The researchers then assessed whether the presence of any of these variants was linked to BMI and being overweight or obese.

Results showed that the two groups had significantly different proportions of the genetic forms of AGT and ACE, tending to show opposing proportions. In particular, the “TT” form of AGT and the “DD” form of ACE were found more frequently in the overweight-obese group.

These two forms were associated with higher frequencies of dyslipidemia, higher values of BMI and waist circumference, and a higher risk of being overweight-obese.

Consistently, the presence of at least one AGT copy with the “M” variant or at least one “I” ACE variant were associated with a lower likelihood of being overweight-obese, and people carrying the “MM” form of AGT or the “II” form of ACE had the lowest risk of being overweight-obese.

“In conclusion, this preliminary case-control study indicates that [AGT and ACE variants] were significantly associated with overweight-obesity, BMI, and dyslipidemia in this sample of the Tunisian population,” the researchers wrote.

The team said that while these findings are consistent with some of the previous studies on the association between AGT and ACE genes and obesity, larger studies are needed to confirm such links.

In addition, future studies assessing the levels and function of AGT and ACE, the proteins coded by the AGT and ACE genes, may help to shed light on their role in obesity, the researchers added.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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