Identifying maternal links to obesity in Arab populations

Mitochondrial DNA (mtDNA) is passed down the maternal line and accumulates mutations over generations. Some variations alter the behaviour of genes linked to metabolism. Crucially, combinations of mtDNA variations are often specific to geographical regions. This means scientists can track different human population groups, or haplogroups, as defined by their mtDNA origins.

“Tracking haplogroups and related genetic variations can help us pinpoint individuals in a given population who are more likely at risk of metabolic disorders,” says Thangavel Thanaraj of the Dasman Diabetes Institute in Kuwait, who worked on both studies. “Mitochondria – the energy metabolism powerhouse – play a central role in regulating metabolic function and flexibility.”  

Haplogroups linked with obesity risk have already been identified in some Western European populations. For example, haplogroup T is related to higher obesity rates in Austria and Italy, while haplogroup X is linked to leaner body mass and lower disease risk in Northern Europeans. The findings by the team show interesting connections between haplogroups in the Middle East and those found elsewhere. 

The researchers extracted mtDNA variations and haplogroups from whole exome data of obese and non-obese individuals from Qatar and Kuwait. As with Northern Europeans, haplogroup X was associated with lower obesity risk in the Qatari population, while haplogroup J (which is closely related to haplogroup T) was associated with higher obesity risk. 

Haplogroup L was identified as the highest risk group in the Kuwaiti population. Thanaraj says this haplogroup has not been previously associated with obesity. 

The mitochondrial variants found in at-risk haplogroups are predominantly involved in cell energy production and also influence gene functioning. 

Molecular pathologist Fahd Al-Mulla, of the Dasman Diabetes Institute, notes that, until now, scientists have largely ignored the role of mitochondrial haplogroups or mtDNA variation in understanding obesity and energy imbalance. To explore this further, the team has begun a large-scale mitochondrial genome project to examine the influence of mtDNA on obesity, diabetes, and related metabolic complications in the Kuwaiti population.

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