Association of mitochondrial haplogroup H with reduced risk of type 2 Diabetes among Gulf Region Arabs.

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  • Additional Information
    • Source:
      Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Lausanne : Frontiers Research Foundation]
    • Subject Terms:
      Diabetes Mellitus, Type 2*/genetics ; Diabetes Mellitus, Type 2*/epidemiology ; Arabs*/genetics ; Haplotypes* ; DNA, Mitochondrial*/genetics; Humans ; Female ; Male ; Middle Aged ; Qatar/epidemiology ; Mitochondria/genetics ; Adult ; Kuwait/epidemiology ; Genetic Predisposition to Disease ; Case-Control Studies ; Risk Factors
    • Abstract:
      Background: Numerous studies have linked mitochondrial dysfunction to the development of type 2 diabetes (T2D) by affecting glucose-stimulated insulin secretion in pancreatic beta cells and reducing oxidative phosphorylation in insulin-responsive tissues. Given the strong genetic underpinnings of T2D, research has explored the connection between mitochondrial DNA haplogroups, specific variants, and the risk and comorbidities of T2D. For example, haplogroups F, D, M9, and N9a have been linked to an elevated risk of T2D across various populations. Additionally, specific mitochondrial DNA variants, such as the rare mtDNA 3243 A>G and the more prevalent mtDNA 16189 T>C, have also been implicated in heightened T2D risk. Notably, these associations vary among different populations. Given the high incidence of T2D in the Gulf Cooperation Council countries, this study investigates the correlation between T2D and mitochondrial haplogroups and variants in Arab populations from the Gulf region.
      Methods: This analysis involved mitochondrial haplogroup and variant testing in a cohort of 1,112 native Kuwaiti and Qatari individuals, comprising 685 T2D patients and 427 controls. Complete mitochondrial genomes were derived from whole exome sequencing data to examine the associations between T2D and haplogroups and mitochondrial DNA variants.
      Results: The analysis revealed a significant protective effect of haplogroup H against T2D (odds ratio [OR] = 0.65; P = 0.022). This protective association persisted when adjusted for age, sex, body mass index (BMI) and population group, with an OR of 0.607 (P = 0.021). Furthermore, specific mitochondrial variants showed significant associations with T2D risk after adjustment for relevant covariates, and some variants were exclusively found in T2D patients.
      Conclusion: Our findings confirm that the maternal haplogroup H, previously identified as protective against obesity in Kuwaiti Arabs, also serves as a protective factor against T2D in Arabs from the Gulf region. The study also identifies mitochondrial DNA variants that either increase or decrease the risk of T2D, underscoring their role in cellular energy metabolism.
      Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
      (Copyright © 2024 Dashti, Ali, Alsaleh, John, Nizam, Thanaraj and Al-Mulla.)
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    • Contributed Indexing:
      Keywords: Arab; haplogroups; mitochondria; mtDNA variants; type 2 diabetes
    • Accession Number:
      0 (DNA, Mitochondrial)
    • Publication Date:
      Date Created: 20241211 Date Completed: 20241211 Latest Revision: 20241219
    • Publication Date:
      20241220
    • Accession Number:
      PMC11628290
    • Accession Number:
      10.3389/fendo.2024.1443737
    • Accession Number:
      39659613