1.Association between Mitofusin 2 Gene Polymorphisms and Late-Onset Alzheimer's Disease in the Korean Population.
Young Jong KIM ; Jin Kyung PARK ; Won Sub KANG ; Su Kang KIM ; Changsu HAN ; Hae Ri NA ; Hae Jeong PARK ; Jong Woo KIM ; Young Youl KIM ; Moon Ho PARK ; Jong Woo PAIK
Psychiatry Investigation 2017;14(1):81-85
OBJECTIVE: Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. METHODS: One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72.3±4.41) and 186 healthy control subjects (82 men and 104 women, mean age 76.5±5.98). RESULTS: Among these three SNPs, rs1042837 showed statistically significant differences in allele frequency, and genotype frequency in the co-dominant 1 model and in the dominant model. CONCLUSION: These results suggest that the rs1042837 polymorphism in MFN2 may be involved in the pathogenesis of AD.
Alzheimer Disease*
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Brain
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Clinical Coding
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Female
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Gene Frequency
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Genotype
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Humans
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Male
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Mitochondrial Dynamics
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Optic Atrophy, Autosomal Dominant
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Polymorphism, Genetic
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Polymorphism, Single Nucleotide
2.The G401D mutation of OPA1 causes autosomal dominant optic atrophy and hearing loss in a Chinese family.
Tie KE ; Shang-wu NIE ; Qin-bo YANG ; Jian-ping LIU ; Lin-na ZHOU ; Xiang REN ; Jing-yu LIU ; Qing WANG ; Mu-gen LIU
Chinese Journal of Medical Genetics 2006;23(5):481-485
OBJECTIVETo describe the clinical and genetic characteristics of a Chinese family affected with optic atrophy 1 (OPA1).
METHODSLinkage analysis and DNA sequencing as well as PCR/restriction fragment length polymorphism (RFLP) analysis were performed to identify the disease-causing mutation.
RESULTSA missense mutation, G401D in the OPA1 gene was identified, and the patients demonstrate inherited syndrome of optic atrophy and hearing loss.
CONCLUSIONThe present study demonstrates that a mutation in the OPA1 gene can cause optic atrophy in Chinese patients, and supports the notion that OPA1 mutation may lead to OPA1 combined with hearing loss.
Adult ; Base Sequence ; Child ; China ; Chromosomes, Human, Pair 3 ; genetics ; DNA Mutational Analysis ; Family Health ; Female ; GTP Phosphohydrolases ; genetics ; Hearing Loss ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Optic Atrophy, Autosomal Dominant ; genetics ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length
3.Bax inhibitor 1 inhibits vascular calcification in mice by activating optic atrophy 1 expression.
Wei Ren CHEN ; Hui DU ; Geng QIAN ; Yu Jie ZHOU ; Yun Dai CHEN ; Qian MA ; Xue Sha WU ; Yuan SHA
Journal of Southern Medical University 2022;42(3):330-337
OBJECTIVE:
To investigate the effects of Bax inhibitor 1 (BI- 1) and optic atrophy protein 1 (OPA1) on vascular calcification (VC).
METHODS:
Mouse models of VC were established in ApoE-deficient (ApoE-/-) diabetic mice by high-fat diet feeding for 12 weeks followed by intraperitoneal injections with Nε-carboxymethyl-lysine for 16 weeks. ApoE-/- mice (control group), ApoE-/- diabetic mice (VC group), ApoE-/- diabetic mice with BI-1 overexpression (VC + BI-1TG group), and ApoE-/- diabetic mice with BI-1 overexpression and OPA1 knockout (VC+BI-1TG+OPA1-/- group) were obtained for examination of the degree of aortic calcification using von Kossa staining. The changes in calcium content in the aorta were analyzed using ELISA. The expressions of Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP-2) were detected using immunohistochemistry, and the expression of cleaved caspase-3 was determined using Western blotting. Cultured mouse aortic smooth muscle cells were treated with 10 mmol/L β-glycerophosphate for 14 days to induce calcification, and the changes in BI-1 and OPA1 protein expressions were examined using Western blotting and cell apoptosis was detected using TUNEL staining.
RESULTS:
ApoE-/- mice with VC showed significantly decreased expressions of BI-1 and OPA1 proteins in the aorta (P=0.0044) with obviously increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P= 0.0041). Overexpression of BI-1 significantly promoted OPA1 protein expression and reduced calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P=0.0006). OPA1 knockdown significantly increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 in the aorta (P=0.0007).
CONCLUSION
BI-1 inhibits VC possibly by promoting the expression of OPA1, reducing calcium deposition and inhibiting osteogenic differentiation and apoptosis of the vascular smooth muscle cells.
Animals
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Apolipoproteins E/metabolism*
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Calcium/metabolism*
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Caspase 3/metabolism*
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Cells, Cultured
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Core Binding Factor Alpha 1 Subunit/metabolism*
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Diabetes Mellitus, Experimental/pathology*
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GTP Phosphohydrolases/metabolism*
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Membrane Proteins/metabolism*
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Mice
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Mice, Knockout
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Muscle, Smooth, Vascular/pathology*
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Myocytes, Smooth Muscle/pathology*
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Optic Atrophy, Autosomal Dominant/pathology*
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Osteogenesis
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Vascular Calcification/pathology*
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bcl-2-Associated X Protein/metabolism*