Abstract
Background: Mitochondrial dysfunction is implicated in the pathogenesis of type 2 diabetes (T2D) via impaired glucose-stimulated insulin secretion in pancreatic beta cells and decreased oxidative phosphorylation in insulin target tissues. Several global studies have been performed to delineate the genetic associations of mitochondrial DNA (mtDNA) haplogroups and variants with T2D incidence. Maternal haplogroups F, D, M9 and N9a and a rare variant (mtDNA 3243 A>G) and a common variant (mtDNA 16189 T>C) were associated with increased risk of T2D in different populations. It is worth noting that some of these proposed associations were not consistent across populations. Since the Gulf Cooperation Council (GCC) countries are marked by high prevalence of T2D, we aim to study association of mitochondrial haplogroups and variants in Arabs from GCC region. Methods: We examined mitochondrial haplogroups and variants in 1,112 Kuwaiti and Qatari native individuals using whole exome sequencing data. The cohort was divided into T2D cases (685) and non-T2D controls (427). Results: The association tests indicated that individuals with haplogroup H have a protective effect against T2D with a suggestive significance [odds ratio (OR) = 0.65; P = 0.022]. The haplogroup H association remained significant even after adjusting for age, sex, and body mass index (BMI) (OR= 0.607; P= 0.021). We also identified mtDNA variants with suggestive significance of association (adjusting for covariates) with T2D. Conclusion: The study demonstrates that maternal H haplogroup, which we previously identified as protective towards obesity in Kuwaiti Arabs, is a protective haplogroup for T2D in Arabs from GCC. Further, the mtDNA variants delineated as associated with T2D are from genes involved in cell energy production. Disclosure M.H.Dashti: None. N.Ali: None. H.Alsaleh: None. R.Nizam: None. F.Almulla: None. A.T.Thangavel: None.
Published Version
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