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The D-loop region comprises three hypervariable regions, namely HVS-I, HVS-II, and HVS-III, and regulates mtDNA transcription and replication. 6 The non-coding control region of the circular mitochondrial DNA (mtDNA) is about 1,200 base pairs in length and known as the displacement loop (D-loop) region. The human mitochondrial genome consists of 37 genes to maintain energy production and storage, encoding 13 mRNA, 2 rRNA, and 22 tRNA. However, few studies have shown the association between impaired mitochondrial function and obesity. Considering the inimitable characteristic features of mitochondrial genome – such as high copy number, high mutation rate, and maternal inheritance – it is not surprising that both inherited and acquired mitochondrial variations and their association with common complex diseases have been widely studied. 3 Mitochondria are the powerhouses of the cell involved in many biological processes and essential for life. 2 A recent study has shown that obesity could possibly be passed from a mother to her child through the mitochondria. Biologically, both these stemming factors lead to improper energy balance in the body, affecting the regular mitochondrial energy metabolism. 1 These alarming health risks could be attributed to constant physical inactivity or sedentary lifestyle, and the high consumption of a calorie-rich diet. 1 It has been shown that obesity increases the risk of comorbid health burdens like diabetes, cardiovascular disease, and cancer among Kuwaiti individuals. In Kuwait, more than 37% of the adults are obese, which is three times higher than the world average obesity rate (13%). Obesity is a disorder defined by the accumulation of surplus body fat, resulting in adverse effects on health. Keywords: obesity, mitochondrial DNA, D-loop, haplogroup, haplotype, SNVs Based on the mtDNA D-loop region variations, we detected particular variants and haplogroup that are related with increased and decreased probability of being obese in the Kuwait Arab population.
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Haplotype analysis revealed that a haplotype, A263G-C309CT-T310C, defining the H2a clade of H haplogroup, reduces the probability of being obese.Ĭonclusion: Our study reports, for the first time, the obesity-related mtDNA variants in Arabs of Kuwait. We found that the variant m.73A>G increases the likelihood of being obese by 6-fold, whereas haplogroup H decreases the probability of being obese in Arab individuals of Kuwait. All these variants, except m.16318A>T, remain statistically significant after adjusting for age and gender. We categorized the individuals based on their BMI scores as obese (n=232 BMI ≥30 kg/m 2), overweight (n=110 BMI ≥25 kg/m 2 and G, and m.523delAC were positively correlated with obesity, while m.310T>C, and m.16318A>T were negatively associated. Materials and methods: We re-sequenced mtDNA displacement loop (D-loop) region of 395 Arab individuals of Kuwait. However, such obesity-associated mtDNA examinations are rarely conducted in Arab populations. *These authors contributed equally to this workīackground: The association of mitochondrial DNA (mtDNA) variations with obesity has been investigated in diverse populations across the world. Muthukrishnan Eaaswarkhanth, 1,* Motasem Melhem, 1,* Prem Sharma, 1 Rasheeba Nizam, 1 Ashraf Al Madhoun, 1 Gyaneshwer Chaubey, 2 Osama Alsmadi, 3 Ebaa AlOzairi, 1 Fahd Al-Mulla 1ġGenetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman, 15462, Kuwait 2Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India 3Department of Cell Therapy & Applied Genomics, King Hussein Cancer Center, Amman, Jordan