THE ASSOCIATION OF MITOCHONDRIAL DNA MUTATION G3316A AND T3394C WITH DIABETES MELLITUS

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ABSTRACT: Mutation in the mitochondrial DNA (mtDNA) is known as a monogenic causative factor for A3243G mtDNA mutation in the pathomechanism of type 2 diabetes mellitus (T2DM). A point mutation at nucleotide position G3316A and T3394C in the mtDNA NADH dehygrogenase 1 (ND1) gene has been reported in T2DM, categorized as Single Nucleotide Polymorphism (SNP. However, those two SNPs have been also found in normal population. The role of mtDNA mutation is still not yet studied widely among Indonesian population. We therefore investigated the contribution of mtDNA mutation and diabetes mellitus (DM). Blood DNA was screened from 451 of T2DM cases collected from DM patients at Dr. Soetomo Hospital during 2001-2003. The G3316A and T3394C were detected using PCR and digested with HaeIII restriction enzyme. Fortunately, we found two pedigrees harboring G3316A and two pedigrees with T3394C point mutation. Family studies of those pedigrees showed that DM with those G3316A and T3394C had a significant odds ratio 5.2 (95% CI: 1.222-2.,134) and 3.185 (95% CI: 1.025-9.893), respectively, compared to the sample taken from the same social and environmental  background. We suggest that there are two types of mtDNA mutation associated with DM. The first is pathogenic mutations that lead to severe defect in oxidative phosphorylation (OXPHOS), represented by A3243G, and thus causal for DM. The second is SNPs that presumably alter tissue capacity for OXPHOS in such a way contributing to the polygenic T2DM as a presponding factor. A conclusion can be made that is G3316A and T3394C are SNPs that have a role as polygenic components to the pathomechanism of DM.  
Keywords:  mithocondrial DNA mutation, monogenic, polygenic, diabetes mellitus, maternally inherited, single nucleotide polymorphism, A3243G, G3316A, T3394C
Author: Agung Pranoto
Journal Code: jpkedokterangg050013

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Jp Kedokteran gg 2005