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Mitochondrial DNA D-loop sequencing reveals obesity variants in an Arab population

Authors Eaaswarkhanth M, Melhem M, Sharma P, Nizam R, Al Madhoun A, Chaubey G, Alsmadi O, AlOzairi E, Al-Mulla F

Received 17 December 2018

Accepted for publication 13 April 2019

Published 24 May 2019 Volume 2019:12 Pages 63—70

DOI https://doi.org/10.2147/TACG.S198593

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer


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-Mulla1

1Genetics 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

*These authors contributed equally to this work

Background:
The association of mitochondrial DNA (mtDNA) variations with obesity has been investigated in diverse populations across the world. However, such obesity-associated mtDNA examinations are rarely conducted in Arab populations.
Materials and methods: We re-sequenced mtDNA displacement loop (D-loop) region of 395 Arab individuals of Kuwait. We categorized the individuals based on their BMI scores as obese (n=232; BMI ≥30 kg/m2), overweight (n=110; BMI ≥25 kg/m2 and <30 kg/m2), and lean (n=53; BMI <25 kg/m2). We performed all the statistical tests by combining obese and overweight individuals in one group. Association analyses were conducted applying Fisher’s exact test and logistic regression model.
Results: We identified that the mtDNA variations m.73A>G, and m.523delAC were positively correlated with obesity, while m.310T>C, and m.16318A>T were negatively associated. All these variants, except m.16318A>T, remain statistically significant after adjusting for age and gender. 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. Haplotype analysis revealed that a haplotype, A263G-C309CT-T310C, defining the H2a clade of H haplogroup, reduces the probability of being obese.
Conclusion: Our study reports, for the first time, the obesity-related mtDNA variants in Arabs of Kuwait. 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.

Keywords: obesity, mitochondrial DNA, D-loop, haplogroup, haplotype, SNVs

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