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Dong Myung Kim, Jin Wook Jeoung, Moon-Woo Seong, Sung Sup Park; Next Generation Sequencing Identifies Novel Variants of Mitochondrial DNA in Normal-Tension Glaucoma Patients. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6235.
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Since up to 21% of normal-tension glaucoma (NTG) patients were reported to have a family history, it is suggested that these patients may be genetically predisposed to developing NTG. In this study, we performed a genetic analysis of the mitochondrial gene and revealed the genetic risk variants in the NTG patients.
DNA was extracted from peripheral blood of the NTG patients and normal control subjects. For the 20 NTG patients (discovery sample), the entire mitochondrial DNA (mtDNA) was sequenced using the next generation sequencing. From these results, we revealed new genetic risk variants for NTG patients. For the candidate genetic variants, we performed a disease-gene association study in the independent case (n=76) - control (n=82) populations (replication sample). For the replication sample, we used the Sanger’s sequencing method.
This study identified 156 different novel mtDNA sequence changes. Of these, 21 sequence variants were identified at the frequency of more than 15%, which were located in the ND2-ND6, RNR1, RNR2, COX1, COX3, ATP6, ATP8, and CYTB genes. For the 21 candidate genetic variants, a disease-gene association study was performed. The frequencies of 12372G>A (ND5 gene) and 14766C>T (CYTB gene) were significantly different between NTG patients and controls (18.9% vs 2.4%, P=0.002; 8.0% vs 0.0%, P=0.028). However, only the association with 12372G>A in ND5 gene resisted to Bonferroni correction for multiple tests.
This study reveals a spectrum of mtDNA variants in patients with NTG. These results suggest that mitochondrial dysfunction may be a risk factor for the development of NTG.
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