Ancient Genetic Adaptations May Explain Increased Risk of Obesity in Modern Kuwait

Ancient Genetic Adaptations May Explain Increased Risk of Obesity in Modern Kuwait
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Evolutionary changes in the genome of ancient Kuwaitis that helped them survive extremely harsh environmental conditions and food scarcity in the Arabian Desert may make the modern Kuwait population — which now has a sedentary lifestyle — more prone to metabolic disorders.

The study with that assertion found a particular genetic region that was more frequent in Kuwaitis than in other populations, and was linked significantly with obesity, high blood pressure, diabetes and asthma — explaining the high incidence of these conditions in Kuwait.

The study, “Genome-Wide Selection Scan in an Arabian Peninsula Population Identifies a TNKS Haplotype Linked to Metabolic Traits and Hypertension,” was published in the journal Genome Biology and Evolution.

Cardiovascular diseases are responsible for about 31% of deaths worldwide; it is the number-one cause of death. But people in Kuwait appear to be disproportionally affected, with 41% of the population dying from cardiovascular causes.

People in Kuwait also are diagnosed more frequently with obesity, diabetes, and high blood pressure, which are all risk factors for cardiovascular disease. But exactly why this happens is unknown.

A recent study examining the natural selection of genes that helped ancient populations of Kuwait adapt to its harsh environmental conditions demonstrated that genetic factors may be contributing to these diseases.

“Our ancestors led a nomadic life, where they regularly moved long distances — either in the desert for camel rearing, or in the sea for fishing — so they burned most of the calories they consumed,” Fahd Al-Mulla, chief scientific officer of the Dasman Diabetes Institute, said in a press release.

“An active metabolism meant that fewer calories were wasted in the harsh, nutrient-scarce desert conditions,” said Al-Mulla, who is the study’s senior  author.

Kuwait is one of seven countries located on the Arabian Peninsula in the coastal region of the Arabian Gulf. Being at the crossroads between Africa and Eurasia, people in this country have a high genetic diversity.

But much as Europeans acquired tolerance to lactose, or most Africans became resistant to malaria, this population is likely to have experienced genetic evolution that helped them adapt to the hot and dry desert climates of the region.

To investigate this further, the team examined the genomes of 583 healthy unrelated Kuwaiti individuals and compared them with those of global populations. They assessed a set of 556,188 genetic variations, which, in this case, represent substitutions of single nucleotides, the building blocks of DNA. Researchers used four distinct statistical methods that measured genetic variations over time.

The four methods retrieved 385 variations that were more frequent in the Kuwaiti population compared to other global populations.

Since genetic variations often are inherited together, researchers examined clusters of DNA that contained at least one of those variations, and identified the genes included in each of the clusters. The resulting 379 genes all fell into one group of biological processes — the chemical reactions involved in the formation of some sugars.

The team then detected a single DNA region that contained seven of the  genetic variations, which also was the most frequent region in people of Kuwait compared to other populations. This region included only one gene — the TNKS gene — that has been linked with increased weight, diabetes, and asthma.

In their analysis, the team also revealed that this region was associated with high blood pressure. “To the best of our knowledge, this is the first report linking the region to hypertension,” the researchers wrote.

Notably, while a similar analysis in a Saudi Arabian population identified genetic regions also associated with metabolic problems, none of these regions were linked to high blood pressure, indicating that this is specific to the Kuwaiti population.

“Our research spots the regions of the genome that might have induced active metabolism and hypertension in nomadic Kuwaiti forefathers, which may favor survival in harsh environments,” said Muthukrishnan Eaaswarkhanth, PhD, the study’s lead author.

“Our findings suggest that past adaptive trends may have further predisposed Kuwaiti populations to the modern metabolic diseases at the genetic level,” Eaaswarkhanth said.

“Overall, the mechanisms through which the TNKS [cluster] conferred a fitness advantage and how the same [cluster] predisposes the population to metabolic diseases remain fascinating areas that could be explored in future research,” the researchers wrote.

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
Total Posts: 9

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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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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