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