Masashi Tanaka

Tokyo Metropolitan Institute of Gerontology, Edo, Tōkyō, Japan

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Publications (214)909 Total impact

  • Eri Miyamoto-Mikami · Noriyuki Fuku · Masashi Tanaka
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    ABSTRACT: Variance in human physiological traits is understood to be the result of both environmental and genetic factors. Indeed, it has been reported that 66 % of the variance in athletic status is explained by genetic factors. Elucidating the substantial genetic contribution to elite athletic performance would enhance our understanding of the limits to human performance and improve methods for detecting sports talent. To date, a number of studies have attempted to identify genetic polymorphisms associated with athletic performance, and the number of genetic polymorphisms associated with physical performance-related phenotypes are increasing every year. In this chapter, we introduce some of these studies focusing on mitochondrial DNA polymorphisms and the two most studied nuclear DNA polymorphisms, namely angiotensin I-converting enzyme (ACE) and α-actinin-3 (ACTN3) polymorphisms.
    Sports Performance, First edition edited by Kazuyuki Kanosue, Tomoyuki Nagami, Jun Tsuchiya, 08/2015: chapter Genetic Polymorphisms Associated with Elite Athlete Status: pages 105-124; Springer Japan.
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    ABSTRACT: Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.
    Journal of aging research 02/2015; 2015:1-7. DOI:10.1155/2015/425261
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    ABSTRACT: Werner syndrome is a rare autosomal recessive disorder caused by mutations in the human WRN gene and characterized by the early onset of normal aging symptoms. Given that patients with this disease exhibit osteoporosis, the present study aimed to determine whether the WRN gene contributes to the etiology of osteoporosis. A genetic association study of eight non-synonymous polymorphisms in the WRN gene and the incidence of femoral fracture was undertaken in 1,632 consecutive Japanese autopsies in which 140 patients had experienced the fracture during their lifetime. The results were validated in 251 unrelated postmenopausal Japanese women with osteoporosis and 269 non-institutionalized, community-dwelling Japanese adults. A statistically significant association was observed between rs2230009 (c.340G > A)-which results in a Val to Ile substitution-and fracture risk; the incidence of femoral fracture increased dose-dependently with the number of A alleles (p = 0.0120). Femoral neck bone and whole bone densities were lower among postmenopausal women with osteoporosis and community-dwelling adults, respectively, if they were of the AG instead of the GG genotype. The results suggest that Japanese subjects bearing at least one A allele of rs2230009 of the WRN gene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density.
    Journal of Bone and Mineral Metabolism 01/2015; DOI:10.1007/s00774-014-0636-0 · 2.11 Impact Factor
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    ABSTRACT: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.
    Molecular Brain 01/2015; 8(1):50. DOI:10.1186/s13041-015-0142-x · 4.35 Impact Factor
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    ABSTRACT: Chromodomain helicase DNA-binding protein 4 (CHD4) plays a pivotal role in chromatin-remodeling and has been implicated in the development of cancer. The aim of this study is to determine the association of CHD4 gene variants with cancer. Nine missense single nucleotide variations (SNVs) in CHD4 were retrieved from genotyping, by an exome-chip, 2,343 consecutive autopsy cases, in which the presence or absence of cancer was pathologically reviewed. The association of CHD4 variants with the presence of cancer and with different types of cancer was determined. Interaction with smoking was also determined. There were 1,446 patients with cancer and 897 patients without cancer. Of the nine SNVs, eight SNVs were monomorphic, while two nonsynonymous SNVs; rs7479004 (p.D140E) and rs1639122 (p.E139D) were further verified by direct sequencing. The p.D140E was associated with the presence of cancer (adjusted odds ratio [OR], 2.17; 95% confidence interval [CI], 1.37–3.44, P = 0.001), but not p.E139D. The effect size was larger in the smokers (adjusted OR, 4.66; 95% CI, 1.82–11.9; P =0.001), suggesting that there may be a gene environment interaction. For individual cancer types, p.D140E was associated with lung cancer (adjusted OR, 3.99; 95% CI, 2.07–7.67; P < 0.001), malignant lymphoma (adjusted OR, 3.24; 95% CI, 1.43–7.33; P = 0.005), and rectum cancer (adjusted OR, 6.23; 95% CI, 2.31–16.8; P < 0.001). A nonsynonymous SNV of CHD4, p.D140E, confers a risk of cancer and may interact with smoking habit to increase the risk. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 11/2014; 54(2). DOI:10.1002/gcc.22227 · 3.84 Impact Factor
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    ABSTRACT: Pyruvate therapy is a promising approach for the treatment of mitochondrial diseases. To identify novel biomarkers for diagnosis and to evaluate therapeutic efficacy, we performed microarray analysis of 2SD cybrid cells harboring a MELAS-causing mutation and control cells treated with either lactate or pyruvate. We found that expression and secretion of growth differentiation factor 15 (GDF15) were increased in 2SD cells treated with lactate and that serum GDF15 levels were significantly higher in patients with mitochondrial diseases than in those with other diseases, suggesting that GDF15 could be a useful marker for diagnosis and evaluating the therapeutic efficacy of pyruvate.
    Mitochondrion 11/2014; 20. DOI:10.1016/j.mito.2014.10.006 · 3.52 Impact Factor
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    ABSTRACT: Individuals born with a low birth weight (LBW) have a higher risk of developing kidney dysfunction during their lifetime and sometimes exhibit focal segmental glomerulosclerosis (FSGS) lesions in their glomeruli. We herein try to obtain other pathological characteristics of LBW-related nephropathy. We retrospectively evaluated the renal pathology of four patients demonstrating FSGS with a history of LBW. Two mitochondrial cytopathy patients were also analyzed. DNA mutations were surveyed using a PCR-Luminex assay. In all four FSGS patients with a history of LBW, focal segmental glomerulosclerosis were detected. Interestingly, granular swollen epithelial cells (GSECs), which have previously been reported exclusively in patients with mitochondrial cytopathy, were also observed in the distal tubules and/or collecting ducts of all four patients with a history of low birth weight in this study. Electron microscopy revealed that these granular swollen epithelial cells included an increased number of enlarged mitochondria. Furthermore, cytochrome c oxidase subunit IV staining of patients with a history of low birth weight and patients with mitochondrial DNA mutations showed unbalanced expression patterns in glomeruli and a part of tubular cells. However, no mitochondrial gene mutations were detected in any of our four patients with low birth weight-related nephropathy. This is the first report to show the pathological similarities not only in glomeruli but also tubuli between nephropathy with a LBW history and nephropathy with mitochondrial cytopathy. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_181
    Diagnostic Pathology 09/2014; 9(1):181. DOI:10.1186/s13000-014-0181-0 · 2.41 Impact Factor
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    ABSTRACT: Genome-wide association studies identified single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) in middle-aged populations; however, it is unclear whether these SNPs are associated with body fatness in elderly people. We examined the association between genetic risk score (GRS) from BMI-associated SNPs and body fatness in elderly Japanese men. We also examined the contribution of GRS, dietary macronutrient intake, and physical activity to body fatness by different age groups. GRS was calculated from 10 BMI-associated SNPs in 84 middle-aged (30-64 years) and 97 elderly (65-79 years) Japanese men; subjects were divided into low, middle, and high GRS groups. Dietary macronutrient intake was assessed using a questionnaire, and physical activity was evaluated using both a questionnaire and an accelerometer. The middle-aged individuals with a high GRS had greater BMI; waist circumference; and total abdominal fat, visceral fat, and subcutaneous fat areas than the middle-aged individuals with low GRS, whereas the indicators were not different between the GRS groups in elderly individuals. Multiple linear regression analysis showed that GRS was the strongest predictor of BMI, total abdominal fat, and visceral fat in the middle-aged group, whereas fat, alcohol, and protein intakes or vigorous-intensity physical activity were more strongly associated with these indicators than was GRS in the elderly group. These results suggest that GRS from BMI-associated SNPs is not predictive of body fatness in elderly Japanese men. The stronger contribution of dietary macronutrient intake and physical activity to body fatness may attenuate the genetic predisposition in elderly men.
    Genes & Nutrition 09/2014; 9(5):416. DOI:10.1007/s12263-014-0416-4 · 3.42 Impact Factor
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    ABSTRACT: Abstract The presence of granular swollen epithelial cells (GSECs) in tubular cells was recently reported to be a specific change associated with mitochondrial cytopathy. However, at present, GSEC is not routinely evaluated. We, in this study, present a case of glomerulosclerosis, in which the presence of GSECs should provide us one clue to understand the pathogenesis of its progressive decline of renal function. A 54-year-old Japanese female, who had been diagnosed with Graves' disease, was referred for the examination and treatment of her proteinuria (5.4 g/gCre at the first visit to our hospital). A kidney biopsy showed 28.6% of the glomeruli to be globally sclerosed and 10.7% of the glomeruli to have completely collapsed. However, according to a light microscopic analysis, all other glomeruli showed an almost normal appearance, except for some slight enlargement. Almost 30% of the interstitium was damaged by fibrosis. Characteristically, GSECs were observed in the medulla collecting ducts. Although she had no symptoms of either myopathy or encephalopathy, no history of stroke-like episodes or difficulty in hearing, her serum concentrations of lactate and pyruvate were both elevated. Therefore, mitochondrial DNA sequencing was performed to assess the etiopathogenesis of her nephropathy. Consequently, a homoplasmic 7501 T > A replacement, which has not been previously reported in patients with renal diseases, was detected. This case suggests that the routine evaluation of GSECs can provide important clues to assess the etiopathogenesis of cryptogenic glomerulosclerosis.
    Renal Failure 08/2014; 36(9):1-5. DOI:10.3109/0886022X.2014.945181 · 0.78 Impact Factor
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    ABSTRACT: High cardiorespiratory fitness (CRF) is associated with a reduced risk of type 2 diabetes mellitus (T2DM) and improved β-cell function; genetic factors also determine these risks. This cross-sectional study investigated whether CRF modifies the association of polygenic risk of T2DM with glucose metabolism in non-diabetic Japanese men. Fasting plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured in 174 Japanese men (age: 20-79 years). β-cell function and insulin resistance were evaluated by calculating HOMA-β and HOMA-IR, respectively. CRF was assessed by measuring maximal oxygen uptake (VO2max). Subjects were divided into the low and high CRF groups within each age group according to the median VO2max. Eleven single nucleotide polymorphisms (SNPs) associated with T2DM were analyzed and used to calculate genetic risk score (GRS); subjects were divided into the low, middle, and high GRS groups. The high GRS group had higher HbA1c levels than the low GRS group in both the low and high CRF groups (p < 0.05). Furthermore, the individuals with a high GRS had a lower HOMA-β than those with a low GRS regardless of CRF (p < 0.05). In multiple linear regression analysis, although GRS was a significant predictor of HbA1c (β = 0.153, p = 0.025), VO2max was also associated with HbA1c (β = -0.240, p = 0.041) independent of GRS. These results suggest that CRF is associated with HbA1c levels independent of GRS derived from T2DM-related SNPs; however, it does not modify the association of GRS with increased HbA1c or impaired β-cell function.
    Physiological Genomics 05/2014; 46(14). DOI:10.1152/physiolgenomics.00027.2014 · 2.81 Impact Factor
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    ABSTRACT: Disorders of oxidative phosphorylation (OXPHOS) cause an increase in the NADH/NAD(+) ratio, which impairs the glycolysis pathway. Treatment with pyruvate is expected to decrease the ratio and thereby restore glycolysis. There are some case reports on the efficacy of pyruvate treatment for mitochondrial diseases. However, few of these reports assessed their results using a standardized scale. We monitored 4 bedridden patients with OXPHOS disorders who continued therapies of 0.5-1.0g/kg/day of sodium pyruvate for more than 12months. The efficacies of these treatments were evaluated with the Newcastle Pediatric Mitochondrial Disease Scale and the Gross Motor Function Measure with 88 items. The ages of the patients at the treatment initiation ranged from 8-100months. Of the 4 patients, 3 exhibited improvements within 1-3months from the initiation of treatment. Among these 3 patients, one maintained the improvement for over 2years. The remaining 2 regressed 3-6months after the initiation of treatment. The blood lactate/pyruvate ratios did not correlate with the efficacy of treatment. Pyruvate was effective even in bedridden patients with OXPHOS disorders, at least in the short term. Clinical trials with more patients and less severe disabilities are necessary to evaluate the long-term efficacy of this treatment. Biomarkers other than lactate and pyruvate need to be identified to biochemically monitor the efficacy of this treatment.
    Molecular Genetics and Metabolism 05/2014; 112(2). DOI:10.1016/j.ymgme.2014.04.008 · 2.83 Impact Factor
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    ABSTRACT: Objective Mitochondrial respiratory chain disorder (MRCD) is an intractable disease of infants with variable clinical symptoms. Our goal was to identify the causative mutations in MRCD patients.Methods The subjects were 90 children diagnosed with MRCD by enzyme assay. We analyzed whole mitochondrial DNA (mtDNA) sequences. A cybrid study was performed in two patients. Whole exome sequencing was performed for one of these two patients whose mtDNA variant was confirmed as non-pathogenic.ResultsWhole mtDNA sequences identified 29 mtDNA variants in 29 patients (13 were previously reported, the other 13 variants and three deletions were novel). The remaining 61 patients had no pathogenic mutations in their mtDNA. Of the 13 patients harboring unreported mtDNA variants, we excluded seven variants by manual curation. Of the remaining six variants, we selected two Leigh syndrome patients whose mitochondrial enzyme activity was decreased in their fibroblasts and performed a cybrid study. We confirmed that m.14439G>A (MT-ND6) was pathogenic, while m.1356A>G (mitochondrial 12S rRNA) was shown to be a non-pathogenic polymorphism. Exome sequencing and a complementation study of the latter patient identified a novel c.55C>T hemizygous missense mutation in the nuclear-encoded gene NDUFA1.InterpretationOur results demonstrate that it is important to perform whole mtDNA sequencing rather than only typing reported mutations. Cybrid assays are also useful to diagnose the pathogenicity of mtDNA variants, and whole exome sequencing is a powerful tool to diagnose nuclear gene mutations as molecular diagnosis can provide a lead to appropriate genetic counseling.
    05/2014; 1(5). DOI:10.1002/acn3.59
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    ABSTRACT: High cardiorespiratory fitness (CRF) is associated with a reduced risk for dyslipidemia; however, blood lipid levels are also affected by individual genetic variations. We performed a cross-sectional study to determine whether CRF modifies polygenic risk for dyslipidemia. Serum levels of triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) were measured in 170 Japanese men (age: 20-79 years). CRF was assessed by measuring maximal oxygen uptake (VO2 max), and subjects were divided into low-fitness and high-fitness groups according to the reference VO2 max value for health promotion in Japan. We analyzed 19 single nucleotide polymorphisms (SNPs) associated with TG, LDL-C, or HDL-C levels. Based on these SNPs, we calculated 3 genetic risk scores (GRSs: TG-GRS, LDL-GRS, and HDL-GRS), and subjects were divided into low, middle, and high groups according to the tertile for each GRS. Serum TG levels of low-fitness individuals were higher in the high and middle TG-GRS groups than in the low TG-GRS group (p < 0.01, p < 0.05, respectively), whereas no differences were detected in the TG levels of high-fitness individuals among the TG-GRS groups. In contrast, the high LDL-GRS group had higher LDL-C levels than did the low LDL-GRS group, and HDL-C levels were lower in the high HDL-GRS group than in the low HDL-GRS group regardless of the fitness level (p < 0.05). These results suggest that high CRF attenuates polygenic risk for hypertriglyceridemia; however, high CRF may not modify the polygenic risk associated with high LDL-C and low HDL-C levels in Japanese men.
    Physiological Genomics 01/2014; 46(6). DOI:10.1152/physiolgenomics.00182.2013 · 2.81 Impact Factor
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    ABSTRACT: Background Disorders of oxidative phosphorylation (OXPHOS) cause an increase in the NADH/NAD+ ratio, which impairs the glycolysis pathway. Treatment with pyruvate is expected to decrease the ratio and thereby restore glycolysis. There are some case reports on the efficacy of pyruvate treatment for mitochondrial diseases. However, few of these reports assessed their results using a standardized scale. Methods We monitored 4 bedridden patients with OXPHOS disorders who continued therapies of 0.5 – 1.0 g/kg/day of sodium pyruvate for more than 12 months. The efficacies of these treatments were evaluated with the Newcastle Pediatric Mitochondrial Disease Scale and the Gross Motor Function Measure with 88 items. Results The ages of the patients at the treatment initiation ranged from 8 – 100 months. Of the 4 patients, 3 exhibited improvements within 1 – 3 months from the initiation of treatment. Among these 3 patients, one maintained the improvement for over 2 years. The remaining 2 regressed 3 – 6 months after the initiation of treatment. The blood lactate/pyruvate ratios did not correlate with the efficacy of treatment. Conclusion Pyruvate was effective even in bedridden patients with OXPHOS disorders, at least in the short term. Clinical trials with more patients and less severe disabilities are necessary to evaluate the long-term efficacy of this treatment. Biomarkers other than lactate and pyruvate need to be identified to biochemically monitor the efficacy of this treatment.
    Molecular Genetics and Metabolism 01/2014; · 2.83 Impact Factor
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    ABSTRACT: The purpose of the present study was to identify mitochondrial DNA (mtDNA) polymorphisms and rare variants that associate with elite Japanese athletic status. Subjects comprised 185 elite Japanese athletes who had represented Japan at international competitions (that is, 100 endurance/middle-power athletes: EMA; 85 sprint/power athletes: SPA) and 672 Japanese controls (CON). The entire mtDNA sequences (16 569 bp) were analyzed by direct sequencing. Nucleotide variants were detected at 1488 sites in the 857 entire mtDNA sequences. A total of 311 variants were polymorphisms (minor allele frequency1% in CON), and the frequencies of these polymorphisms were compared among the three groups. The EMA displayed excess of seven polymorphisms, including subhaplogroup D4e2- and D4g-specific polymorphisms, compared with CON (P<0.05), whereas SPA displayed excess of three polymorphisms and dearth of nine polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, compared with CON (P<0.05). The frequencies of 10 polymorphisms, including haplogroup G- and subhaplogroup G2a-specific polymorphisms, were different between EMA and SPA (P<0.05): although none of these polymorphisms differed significantly between groups after correcting for multiple comparison (false discovery rate q-value0.05). The number of rare variants in the 12S ribosomal RNA and NADH dehydrogenase subunit I genes were also higher in SPA than in CON (P<0.05). Analysis of the entire mtDNA of elite Japanese athletes revealed several haplogroup- and subhaplogroup-specific polymorphisms to be potentially associated with elite Japanese athletic status.Journal of Human Genetics advance online publication, 10 October 2013; doi:10.1038/jhg.2013.102.
    Journal of Human Genetics 10/2013; 58(12). DOI:10.1038/jhg.2013.102 · 2.53 Impact Factor
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    ABSTRACT: Background Senescence-accelerated mice (SAM) are a series of mouse strains originally derived from unexpected crosses between AKR/J and unknown mice, from which phenotypically distinct senescence-prone (SAMP) and -resistant (SAMR) inbred strains were subsequently established. Although SAMP strains have been widely used for aging research focusing on their short life spans and various age-related phenotypes, such as immune dysfunction, osteoporosis, and brain atrophy, the responsible gene mutations have not yet been fully elucidated. Results To identify mutations specific to SAMP strains, we performed whole exome sequencing of 6 SAMP and 3 SAMR strains. This analysis revealed 32,019 to 38,925 single-nucleotide variants in the coding region of each SAM strain. We detected Ogg1 p.R304W and Mbd4 p.D129N deleterious mutations in all 6 of the SAMP strains but not in the SAMR or AKR/J strains. Moreover, we extracted 31 SAMP-specific novel deleterious mutations. In all SAMP strains except SAMP8, we detected a p.R473W missense mutation in the Ldb3 gene, which has been associated with myofibrillar myopathy. In 3 SAMP strains (SAMP3, SAMP10, and SAMP11), we identified a p.R167C missense mutation in the Prx gene, in which mutations causing hereditary motor and sensory neuropathy (Dejerine-Sottas syndrome) have been identified. In SAMP6 we detected a p.S540fs frame-shift mutation in the Il4ra gene, a mutation potentially causative of ulcerative colitis and osteoporosis. Conclusions Our data indicate that different combinations of mutations in disease-causing genes may be responsible for the various phenotypes of SAMP strains.
    BMC Genomics 04/2013; 14(1):248. DOI:10.1186/1471-2164-14-248 · 4.04 Impact Factor
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    Noriyuki Fuku · Eri Mikami · Masashi Tanaka
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    ABSTRACT: A number of familial and twin studies have assessed the relative contribution of ge-netic and environmental factors to physical performance or its-related traits and have estimated that there is a significant genetic component to their phenotypes. In addition, aerobic capacity has been found to have stronger maternal inheritance than paternal. This finding implies that functional differences in maternally inherited mtDNA-encoded proteins involved in oxidative phosphorylation affect aerobic performance. In this article, therefore, we focus on associa-tions between mtDNA polymorphisms/haplogroups and elite Japanese athlete status. From sequencing analysis of the control region in the mtDNA, certain mtDNA polymorphisms and haplogroups were shown to be associated with elite Japanese endurance athlete status, prob-ably due to enhanced ATP production by mitochondria in the cardiac and skeletal muscles or both. This phenomenon is in agreement with several previous reports on Caucasian and African populations. It should be noted that certain mtDNA polymorphisms or haplogroups are also associated with elite Japanese sprint athlete/power status, probably due to enhanced calcium dynamics in the skeletal muscle. Thus, mtDNA polymorphisms/haplogroups influence not only aerobic performance but also anaerobic performance.
    04/2013; 2:17-27. DOI:10.7600/jpfsm.2.17
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    ABSTRACT: We previously reported 2 osteoporosis-susceptibility genes-formiminotransferase N-terminal sub-domain containing gene (FONG) and thrombospondin, type 1, domain-containing 7A (THSD7A)-in which we identified two common single-nucleotide polymorphisms, rs7605378 (FONG) and rs12673692 (THSD7A). The former was associated with a predisposition to osteoporosis and the latter with bone mineral density. To further elucidate the importance of these polymorphisms in the pathogenesis of osteoporosis, we examined their association with the incidence of vertebral fracture. DNA extracted from the renal cortex of 2427 consecutive Japanese autopsies (1331 men, mean age: 79 years; 1096 women, mean age: 82 years) were examined in this study. The presence or absence of vertebral fracture during each subject's lifetime was determined by a thorough examination of the clinical records, as well as autopsy reports. After adjustments for sex and age at autopsy, logistic regression analysis revealed that homozygotes for the risk alleles of rs7605378 (A-allele) or rs12673629 (A-allele) possess an increased risk of vertebral fracture. The subjects simultaneously homozygous for both the risk alleles of rs7605378 (AA genotype) and rs12673629 (AA genotype) showed significantly higher risk of vertebral fracture (odds ratio 2.401, 95% confidence interval 1.305-4.416, P=0.0048) than those who had at least one non-risk allele of either rs7605378 (AC/CC genotypes) or rs12673629 (AG/GG genotypes). The results suggest that Japanese subjects homozygous for the risk alleles of rs7605378 and rs12673629 have a higher risk of vertebral fracture.Journal of Human Genetics advance online publication, 10 January 2013; doi:10.1038/jhg.2012.145.
    Journal of Human Genetics 01/2013; 58(2). DOI:10.1038/jhg.2012.145 · 2.53 Impact Factor
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    ABSTRACT: PURPOSE: Polymorphic variation in the angiotensin-converting enzyme (ACE) and α-actinin-3 (ACTN3) genes has been reported to be associated with endurance and/or power-related human performance. Our aim was to investigate whether polymorphisms in ACE and ACTN3 are associated with elite swimmer status in Caucasian and East Asian populations. METHODS: ACE I/D and ACTN3 R577X genotyping was carried out for 200 elite Caucasian swimmers from European, Commonwealth, Russian and American cohorts (short and middle distance, SMD ≤ 400 m, n = 130; long distance, LD > 400 m, n = 70) and 326 elite Japanese and Taiwanese swimmers (short distance, SD ≤ 100 m, n = 166; middle distance, MD: 200 - 400 m, n = 160). Genetic associations were evaluated by logistic regression and other tests accommodating multiple testing adjustment. RESULTS: ACE I/D was associated with swimmer status in Caucasians, with the D-allele being overrepresented in SMD swimmers under both additive and I-allele dominant models (permutation test p = 0.003 and p = 0.0005, respectively). ACE I/D was also associated with swimmer status in East Asians. In this group, however, the I-allele was overrepresented in the SD swimmer group (permutation test p = 0.041 and p = 0.0098 under the additive and the D-allele-dominant models, respectively). ACTN3 R577X was not significantly associated with swimmer status in either Caucasians or East Asians. CONCLUSIONS: ACE I/D associations were observed in these elite swimmer cohorts, with different risk alleles responsible for the associations in swimmers of different ethnicities. The functional ACTN3 R577X polymorphism did not show any significant association with elite swimmer status, despite numerous previous reports of associations with 'power/sprint' performance in other sports.
    Medicine and science in sports and exercise 11/2012; DOI:10.1249/MSS.0b013e31827c501f · 4.46 Impact Factor
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    ABSTRACT: Hearing loss (HL) is the most common sensory disorder in humans. Many patients with mitochondrial diseases have sensorineural HL (SNHL). The HL of these patients manifests as a consequence of either syndromic or nonsyndromic mitochondrial diseases. Furthermore, the phenotypes vary among patients even if they are carrying the same mutation. Therefore, these features make it necessary to analyze every presumed mutation in patients with hereditary HL, but the extensive analysis of various mutations is laborious. We analyzed 373 patients with suspected hereditary HL by using an extended suspension-array screening system for major mitochondrial DNA (mtDNA) mutations, which can detect 32 other mtDNA mutations in addition to the previously analyzed 29 mutations. In the present study, we detected 2 different mtDNA mutations among these 373 patients; m.7444G>A in the MT-CO1 gene and m.7472insC in the MT-TS1 gene in 1 patient (0.3%) for each. As these two patients had no clinical features other than HL, they had not been suspected of having mtDNA mutations. This extended screening system together with the previous one is useful for the genetic diagnosis and epidemiological study of both syndromic and nonsyndromic HL.Journal of Human Genetics advance online publication, 13 September 2012; doi:10.1038/jhg.2012.109.
    Journal of Human Genetics 09/2012; 57(12). DOI:10.1038/jhg.2012.109 · 2.53 Impact Factor

Publication Stats

8k Citations
909.00 Total Impact Points

Institutions

  • 2005–2015
    • Tokyo Metropolitan Institute of Gerontology
      Edo, Tōkyō, Japan
  • 2008–2014
    • Tokyo Metropolitan Institute
      Edo, Tōkyō, Japan
    • Mie University
      • Life Science Research Center
      Tsu-shi, Mie-ken, Japan
  • 2011
    • Waseda University
      • Graduate School of Sport Sciences
      Tokyo, Tokyo-to, Japan
  • 2004
    • National Institute of Health and Nutrition
      Edo, Tōkyō, Japan
    • Tokyo Institute of Technology
      • Department of Life Science
      Edo, Tōkyō, Japan
  • 1980–2003
    • Nagoya University
      • • Department of Natural Science Informatics
      • • Division of Biological Chemistry
      • • Division of Ophtalmology
      Nagoya, Aichi, Japan
  • 1994
    • Okayama University
      • Department of Chemistry
      Okayama, Okayama, Japan
  • 1990
    • Aichi Medical University
      • School of Medicine
      Okazaki, Aichi, Japan