Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population.

This study aimed to examine how genetic polymorphisms related to muscular strength and flexibility influence artistic gymnastic performance in an attempt to identify a novel polymorphism associated with flexibility. In study 1, the passive straight-leg-raise (PSLR) score and aromatase gene CYP19A1 rs936306 polymorphism, a key enzyme for estrogen biosynthesis, were assessed in 278 individuals. In study 2, athletes (281 gymnasts and 1908 other athletes) were asked about their competition level, and gymnasts were assessed using the difficulty score (D-score) for each event. Muscular strength- (ACTN3 R577X rs1815739 and ACE I/D rs4341) and flexibility-related (ESR1 rs2234693 T/C and CYP19A1 rs936306 C/T) genetic polymorphisms were analyzed. In study 1, males with the CYP19A1 CT + TT genotype showed significantly higher PSLR scores than those with the CC genotype. In study 2, male gymnasts with the R allele of ACTN3 R577X showed a correlation with the floor, rings, vault, and total D-scores. In addition, male gymnasts with the C allele of ESR1 T/C and T allele of CYP19A1 C/T polymorphisms were correlated with the pommel horse, parallel bars, horizontal bar, and total D-scores. Furthermore, genotype scores of these three polymorphisms correlated with the total D-scores and competition levels in male gymnasts. In contrast, no such associations were observed in female gymnasts. Our findings suggest that muscular strength- and flexibility-related polymorphisms play important roles in achieving high performance in male artistic gymnastics by specifically influencing the performance of events that require muscular strength and flexibility, respectively.HighlightsEstrogen-related CYP19A1 polymorphism is a novel determinant of flexibility in males.Muscular strength- and flexibility-related polymorphisms play important roles in high performance in male artistic gymnastics.Genotypes of ACTN3 R577X, ESR1 rs2234693, and CYP19A1 rs936306 may contribute to training plan optimization and event selection in artistic gymnastics.

Genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity after prolonged running in men.

This study aimed to clarify 1) the influence of genetic polymorphisms in the cytochrome P450 aromatase gene (CYP19A1) on circulating estradiol levels in men and 2) whether estrogen-related genetic polymorphisms, such as the CYP19A1 rs936306 and estrogen receptor-α (ESR1) rs2234693 polymorphisms, predict exercise-induced serum creatine kinase (CK) activity, which is an index of skeletal muscle membrane disruption. Serum estradiol levels were examined in young men (n = 167). In a different cohort, serum CK activity was analyzed in a 2-day ultramarathon race: baseline, after the first day, and after the second day (114 males and 25 females). Genetic polymorphisms in CYP19A1 rs936306 C/T and ESR1 rs2234693 T/C were analyzed using the TaqMan SNP Genotyping Assay. Male subjects with the TT genotype of the CYP19A1 polymorphism exhibited significantly higher serum estradiol levels than the C allele carriers. Male runners had significantly higher postrace serum CK activity than female runners. The change in the CK activity during the ultramarathon race was significantly lower in male subjects with the CYP19A1 TT genotype than in those with the CC + CT genotypes and was correlated with the number of C alleles in ESR1 rs2234693 in male subjects. Furthermore, the genotype scores of these two polymorphisms were significantly correlated with changes in serum CK activity during race (r = -0.279, P = 0.003). The results of this study suggest that genetic polymorphisms in CYP19A1 rs936306 influence serum estradiol levels in men, and genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity in men.NEW & NOTEWORTHY Men with the TT genotype of the CYP19A1 polymorphism exhibited higher circulating estradiol levels than the TC + CC genotype. The TT genotype in the CYP19A1 polymorphism and the C allele of the ESR1 polymorphism, an allele increasing ESR1 expression, were associated with low serum CK activity after the ultramarathon. A combination of these polymorphisms was correlated with changes in the serum CK activity. Therefore, estrogen-related genetic polymorphisms partially predict exercise-induced muscle damage, that is, skeletal muscle membrane disruption.

A rs936306 C/T Polymorphism in the CYP19A1 Is Associated With Stress Fractures.

ABSTRACT: Kumagai, H, Miyamoto-Mikami, E, Kikuchi, N, Kamiya, N, Zempo, H, and Fuku, N. A rs936306 C/T polymorphism in the CYP19A1 is associated with stress fractures. J Strength Cond Res 36(8): 2322-2325, 2022-A stress fracture (SF) is an overuse injury, and low bone mineral density (BMD) is the risk factor for the SF. Estrogen is suggested to have a crucial role in bone metabolism, and estrogen-related genetic polymorphisms are associated with BMD. However, the possible association between SF and estrogen-related genetic polymorphisms has not been clarified yet. Therefore, we aimed to clarify whether estrogen-related genetic polymorphisms are associated with a history of SFs in Japanese athletes. A total of 1,311 (men: n = 868, women: n = 443) top-level Japanese athletes who participated in various sports and at different levels were analyzed. The history of SFs was assessed using a questionnaire, and the cytochrome P450 aromatase gene ( CYP19A1 ) rs936306 C/T and estrogen receptor α gene ( ESR1 ) rs2234693 T/C polymorphisms were analyzed using the TaqMan genotyping assay. The genotype frequency of the CYP19A1 C/T polymorphism was significantly different between the injured group and noninjured group under the C allele additive genetic model (odds ratio = 1.31, 95% confidence interval = 1.01-1.70), especially in men and in women with irregular menstruation. On the other hand, there were no significant differences with the ESR1 T/C polymorphism. This study demonstrated that the C allele in the CYP19A1 rs936306 polymorphism is a risk factor for SFs in top-level Japanese athletes.

Engagement in different sport disciplines during university years and risk of locomotive syndrome in older age: J-Fit+ Study.

BACKGROUND: Among former Olympic-level athletes, engagement in different sport disciplines has been associated with mortality risk in subsequent years. However, limited evidence is available on whether engagement in different sport disciplines at a young age is associated with locomotive syndrome (LS) risk later in life. This study examined the relationship between engagement in different sport disciplines during university years and LS risk in older age among former university athletes. METHODS: Participants were 274 middle-aged and 294 older men alumni who graduated from a school of physical education in Japan. LS risk was defined as answering "yes" to any of the Loco-check questions. Data on university sports club membership were collected using questionnaires. University clubs were classified into three groups of cardiovascular intensity (low, moderate, high), following the classification system of sport disciplines by the American College of Cardiology. This classification considers the static and dynamic components of an activity, which correspond to the estimated percent of maximal voluntary contraction reached and maximal oxygen uptake achieved, respectively. University clubs were grouped based on the risk of bodily collision (no, yes) and extent of physical contact (low, moderate, high). Relationships between engagement in different sport disciplines and LS risk were analyzed using Cox proportional hazards models, and adjusted for age, height, weight, joint disease, habitual exercise, and smoking and drinking status. RESULTS: Adjusted hazard ratios and 95% confidence intervals associated with the low, moderate, and high cardiovascular intensity sports were 1.00 (reference), 0.48 (0.22-1.06, P = 0.070), and 0.44 (0.20-0.97, P = 0.042) in older men, respectively; however, there was no significant association between these parameters among middle-aged men. Engagement in sports associated with physical contact and collision did not affect LS risk in either group. CONCLUSIONS: Engagement in sports associated with high cardiovascular intensity during university years may reduce the risk of LS in later life. Encouraging young people to participate in such activities might help reduce LS prevalence among older populations.

Female Athletes Genetically Susceptible to Fatigue Fracture Are Resistant to Muscle Injury: Potential Role of COL1A1 Variant.

PURPOSE: We aimed to investigate the hypothesis that type I collagen plays a role in increasing bone mineral density (BMD) and muscle stiffness, leading to low and high risks of fatigue fracture and muscle injury, respectively, in athletes. As a potential mechanism, we focused on the effect of the type I collagen alpha 1 chain gene (COL1A1) variant associated with transcriptional activity on bone and skeletal muscle properties. METHODS: The association between COL1A1 rs1107946 and fatigue fracture/muscle injury was evaluated in Japanese athletes. Effects of the polymorphism on tissue properties (BMD and muscle stiffness) and type I collagen α1/α2 chain ratios in muscles were examined in Japanese nonathletes. RESULTS: The C-allele carrier frequency was greater in female athletes with fatigue fracture than in those without (odds ratio = 2.44, 95% confidence interval [CI] = 1.17-5.77) and lower in female athletes with muscle injury than in those without (odds ratio = 0.46, 95% CI = 0.24-0.91). Prospective validation analysis confirmed that in female athletes, muscle injury was less frequent in C-allele carriers than in AA genotype carriers (multivariable-adjusted hazard ratio = 0.27, 95% CI = 0.08-0.96). Among female nonathletes, the C-allele of rs1107946 was associated with lower BMD and lower muscle stiffness. Muscle biopsy revealed that C-allele carriers tended to have a larger type I collagen α1/α2 chain ratio than AA genotype carriers (2.24 vs 2.05, P = 0.056), suggesting a higher proportion of type I collagen α1 homotrimers. CONCLUSION: The COL1A1 rs1107946 polymorphism exerts antagonistic effects on fatigue fracture and muscle injury among female athletes by altering the properties of these tissues, potentially owing to increased levels of type I collagen α1 chain homotrimers.

A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

Genotype Score for Iron Status Is Associated with Muscle Fiber Composition in Women.

Human muscle fiber composition is heterogeneous and mainly determined by genetic factors. A previous study reported that experimentally induced iron deficiency in rats increases the proportion of fast-twitch muscle fibers. Iron status has been reported to be affected by genetic factors. As the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms are strongly associated with iron status in humans, we hypothesized that the genotype score (GS) based on these polymorphisms could be associated with the muscle fiber composition in humans. Herein, we examined 214 Japanese individuals, comprising of 107 men and 107 women, for possible associations of the GS for iron status with the proportion of myosin heavy chain (MHC) isoforms (I, IIa, and IIx) as markers of muscle fiber composition. No statistically significant correlations were found between the GS for iron status and the proportion of MHC isoforms in all participants. When the participants were stratified based on sex, women showed positive and negative correlations of the GS with MHC-IIa (age-adjusted p = 0.020) and MHC-IIx (age-adjusted p = 0.011), respectively. In contrast, no correlation was found in men. In women, a 1-point increase in the GS was associated with 2.42% higher MHC-IIa level and 2.72% lower MHC-IIx level. Our results suggest that the GS based on the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms for iron status is associated with muscle fiber composition in women.

The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis.

PURPOSE: Iron is an important component of the oxygen-binding proteins and may be critical to optimal athletic performance. Previous studies have suggested that the G allele of C/G rare variant (rs1799945), which causes H63D amino acid replacement, in the HFE is associated with elevated iron indexes and may give some advantage in endurance-oriented sports. The aim of the present study was to investigate the association between the HFE H63D polymorphism and elite endurance athlete status in Japanese and Russian populations, aerobic capacity and to perform a meta-analysis using current findings and three previous studies. METHODS: The study involved 315 international-level endurance athletes (255 Russian and 60 Japanese) and 809 healthy controls (405 Russian and 404 Japanese). Genotyping was performed using micro-array analysis or by PCR. VO2max in 46 male Russian endurance athletes was determined using gas analysis system. RESULTS: The frequency of the iron-increasing CG/GG genotypes was significantly higher in Russian (38.0 vs 24.9%; OR 1.85, P = 0.0003) and Japanese (13.3 vs 5.0%; OR 2.95, P = 0.011) endurance athletes compared to ethnically matched controls. The meta-analysis using five cohorts (two French, Japanese, Spanish, and Russian; 586 athletes and 1416 controls) showed significant prevalence of the CG/GG genotypes in endurance athletes compared to controls (OR 1.96, 95% CI 1.58-2.45; P = 1.7 × 10-9). Furthermore, the HFE G allele was associated with high V̇O2max in male athletes [CC: 61.8 (6.1), CG/GG: 66.3 (7.8) ml/min/kg; P = 0.036]. CONCLUSIONS: We have shown that the HFE H63D polymorphism is strongly associated with elite endurance athlete status, regardless ethnicities and aerobic capacity in Russian athletes.

ESR1 rs2234693 Polymorphism Is Associated with Muscle Injury and Muscle Stiffness.

PURPOSE: Muscle injury is the most common sports injury. Muscle stiffness, a risk factor for muscle injury, is lower in females than in males, implying that sex-related genetic polymorphisms influence muscle injury associated with muscle stiffness. The present study aimed to clarify the associations between two genetic polymorphisms (rs2234693 and rs9340799) in the estrogen receptor 1 gene (ESR1) and muscle injury or muscle stiffness. METHODS: In study 1, a questionnaire was used to assess the muscle injury history of 1311 Japanese top-level athletes. In study 2, stiffness of the hamstring muscles was assessed using ultrasound shear wave elastography in 261 physically active young adults. In both studies, rs2234693 C/T and rs9340799 G/A polymorphisms in the ESR1 were analyzed using the TaqMan SNP Genotyping Assay. RESULTS: In study 1, genotype frequencies for ESR1 rs2234693 C/T were significantly different between the injured and noninjured groups in a C-allele dominant (CC + CT vs TT: odds ratio, 0.62; 95% confidence interval, 0.43-0.91) and additive (CC vs CT vs TT: odds ratio, 0.70; 95% confidence interval, 0.53-0.91) model in all athletes. In study 2, hamstring muscle stiffness was lower in subjects with the CC + CT genotype than in those with the TT genotype; a significant linear trend (CC < CT < TT) was found (r = 0.135, P = 0.029). In contrast, no associations were observed between ESR1 rs9340799 G/A and muscle injury or stiffness. CONCLUSIONS: Our results suggest that the ESR1 rs2234693 C allele, in contrast to the T allele, provides protection against muscle injury by lowering muscle stiffness.

Epistasis, physical capacity-related genes and exceptional longevity: FNDC5 gene interactions with candidate genes FOXOA3 and APOE.

BACKGROUND: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population. A total of 1565 individuals were studied, subdivided into 822 middle-aged controls and 743 centenarians. RESULTS: We found a FOXOA3 rs2802292 T-allele-dependent association of fibronectin type III domain-containing 5 (FDNC5) rs16835198 with EL: the frequency of carriers of the FOXOA3 rs2802292 T-allele among individuals with the rs16835198 GG genotype was significantly higher in cases than in controls (P < 0.05). On the other hand, among non-carriers of the APOE 'risk' ε4-allele, the frequency of the FDNC5 rs16835198 G-allele was higher in cases than in controls (48.4% vs. 43.6%, P < 0.05). Among carriers of the 'non-risk' APOE ε2-allele, the frequency of the rs16835198 G-allele was higher in cases than in controls (49% vs. 37.3%, P < 0.05). CONCLUSIONS: The association of FDNC5 rs16835198 with EL seems to depend on the presence of the FOXOA3 rs2802292 T-allele and we report a novel association between FNDC5 rs16835198 stratified by the presence of the APOE ε2/ε4-allele and EL. More research on 'gene*gene' and 'gene*environment' effects is needed in the field of EL.

A Mechanism Underlying Preventive Effect of High-Intensity Training on Colon Cancer.

INTRODUCTION: We examined effects of high-intensity training on chemically induced aberrant crypt foci (ACF) in rat colon. We also investigated mechanisms that may underlie the results obtained, with a focus on secreted protein acidic and rich in cysteine (SPARC), which has been proposed as an exercise-related factor of colon cancer prevention. METHODS: After an administration of 1,2-dimethylhydrazine, F344 rats executed high-intensity intermittent swimming training (HIIST) (twelve 20-s swimming with a weight [16% body weight] with 10-s pauses between the bouts) 5 d·wk for 4 wk. The acute and chronic effects of the HIIST on SPARC were evaluated in rats. We evaluated the in vitro and in vivo effects of 5' AMP-activated protein kinase (AMPK) activator on SPARC in rat serum and epitrochlearis muscle. In human subjects, we determined serum SPARC after exhaustive bicycling consisting of six to seven bouts of exercise at 170% V˙O2max with 10-s rests between the bouts (high-intensity intermittent bicycling [HIIB]). The SPARC mRNA in human vastus lateralis was measured before and after the HIIB for 4 d·wk for 6 wk (HIIB-training [HIIBT]). RESULTS: The numbers of ACF were lower in the HIIST (47 ± 22) compared with the control (122 ± 47) rats (P < 0.05). SPARC in epitrochlearis and serum after HIIS of the trained rat was higher than that in the control resting rats. In vitro and vivo AMPK stimulation increased mRNA and SPARC protein in rat epitrochlearis, respectively. The human serum SPARC after the HIIB was elevated. SPARC mRNA in human muscle was elevated after the HIIBT. CONCLUSIONS: The results demonstrated that HIIST inhibits 1,2-dimethylhydrazine-induced colon ACF development. This effect may be explained by SPARC induction by the exercise intensity-related factor AMPK, potentially explaining the preventive effects of high-intensity intermittent exercise training against colon cancer.

rs2802292 polymorphism in the FOXO3A gene and exceptional longevity in two ethnically distinct cohorts.

OBJECTIVES: Previous studies have indicated that the rs2802292 polymorphism in the human forkhead box O3A (FOXO3A) gene might be associated with exceptional longevity (EL, i.e., living 100+ years), although the results are conflicting. STUDY DESIGN AND MAIN OUTCOME MEASURES: Using a case-control design, we investigated the distribution of the rs2802292 polymorphism in two ethnically distinct cohorts of centenarians (cases) and younger adults (controls). The first cohort included Japanese individuals (733 centenarians and 820 controls) and the second was from Northern Italy (79 disease-free centenarians and 316 controls). RESULTS: No statistically significant association was found between the rs2802292 polymorphism and EL in either cohort (either examined in their entirety or in a sex-based analysis). CONCLUSIONS: In light of our negative findings, further research and resequencing efforts are needed to shed more light on the potential association between EL and FOXO3A polymorphisms.

No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes.

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.

The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity?

Mitochondrial-derived peptides (MDP) are encoded by functional short open reading frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently discovered mitochondrial open reading frame of the 12S rRNA-c (MOTS-c). Although more research is needed, we suggest that the m.1382A>C polymorphism located in the MOTS-c encoding mtDNA, which is specific for the Northeast Asian population, may be among the putative biological mechanisms explaining the high longevity of Japanese people.

FTO genotype and adiposity in children: physical activity levels influence the effect of the risk genotype in adolescent males.

Studies of the fat mass and obesity-associated (FTO) gene provide compelling evidence of genetic variation in the general population that influences fat levels and obesity risk. Studies of the interaction between genetic and environmental factors such as physical activity (PA) will promote the understanding of how lifestyle can modulate genetic contributions to obesity. In this study, we investigated the effect of FTO genotype, and interactions with PA or energy intake, in young children and adolescents. In all, 1-5-year-old children from the Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) study (N=1980) and 11-18-year-old Greek adolescents (N=949) were measured for adiposity-related phenotypes and genotyped at the FTO single-nucleotide polymorphism (SNP) marker, rs17817449. Adolescents were classified as physically active or inactive based on self-reported levels of PA. In adolescents, FTO genotype influenced weight (P=0.001) and BMI (P=0.007). There was also a significant SNP(*)PA(*)gender interaction (P=0.028) on BMI, which reflected the association between FTO genotype and BMI in males (P=0.016), but not females (P=0.15), and significant SNP(*)PA interaction in males (P=0.007), but not females (P=0.74). The FTO genotype effect was more pronounced in inactive than active males. Inactive males homozygous for the G allele had a mean BMI 3 kg/m(2) higher than T carriers (P=0.008). In the GENESIS study, no significant association between FTO genotype and adiposity was found. The present findings highlight PA as an important factor modifying the effect of FTO genotype.

Macrophages that survive hyperoxia exposure have higher superoxide dismutase activities in their mitochondria.

Prolonged exposure to hyperoxia, which is routinely used in patients with severe respiratory failure, leads to the generation of excessive reactive oxygen species, resulting in lung injury. In the present study, we focused on macrophages and their survival, superoxide dismutase (SOD) activity in mitochondria (Mn-SOD activity), and mitochondrial DNA (mtDNA) mutation after exposure to hyperoxia. Macrophages were cultured under two different conditions: normoxia and intermittent hyperoxia. The number of cells exposed to intermittent hyperoxia for 3 weeks significantly decreased, compared with the number of cells exposed to normoxia. The Mn-SOD activity of the cells that survived intermittent hyperoxia exposure was significantly higher than that of the cells exposed to normoxia. Direct sequencing and a PCR-RFLP assay did not provide any evidence of mutation in the cells that survived intermittent hyperoxia exposure. In conclusion, an increase in the antioxidative activity of mitochondria is important for the survival of macrophages exposed to hyperoxia, and the increased activity level possibly enhances protective effects against mtDNA mutations in surviving cells.

Effect of running training on DMH-induced aberrant crypt foci in rat colon.

PURPOSE: We examined the effects of treadmill-running training on the induction of aberrant crypt foci (ACF), which is the first step of colon cancer induction, in the colonic mucosa of rats injected with 1,2-dimethylhydrazine (DMH). METHODS: Four-week-old F344 rats (N = 38) were randomly assigned to training (19 rats) and control (19 rats) groups. After a week, all rats were given DMH (20 mg.kg(-1) body weight) once a week for 2 wk. Running training was started at age 7 wk (speed: 10 m.min(-1), 0% grade, 120 min.d(-1), 5 d.wk(-1)). After 4 wk of training, the rats were sacrificed and the colon was removed, opened, and counted for ACF with 0.2% methylene blue staining. RESULTS: Running training resulted in lower body- (P < 0.01) and adipose fat weight (P < 0.05). The numbers of ACF and total AC were significantly lower in the running training group than in the control group (P < 0.05). The occurrences of one, three, and five aberrant crypts per focus were also significantly lower in the running training group than in the control group (P < 0.05). The ratios of total AC/ACF did not significantly differ between the running training and control groups. CONCLUSIONS: The results of the present investigation suggest that low-intensity running training inhibits the DMH-induced initiation of colon ACF development.

Mitochondrial haplogroup N9b is protective against myocardial infarction in Japanese males.

Superoxide, which mitochondria mainly produce in vascular endothelial cells, plays an important role in the pathogenesis of atherosclerosis and coronary artery disease. Accordingly, mitochondrial functional differences are thought to be one of the most important factors for the risk of myocardial infarction among various individuals. In the present study, we surveyed mitochondrial haplogroups associated with myocardial infarction in Japanese subjects. The study population comprised 2,137 unrelated Japanese individuals, including 1,181 subjects with a first myocardial infarction (920 males, 261 females) and the control subjects (522 males, 434 females). Twenty-eight mitochondrial single nucleotide polymorphisms of 12 major mitochondrial haplogroups (A, B, D4, D5, F, G1, G2, M7a, M7b, M7c, N9a, and N9b) were determined by use of 28-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes. After adjustment for age, sex, body mass index, and prevalence of smoking, hypertension, hypercholesterolemia, and type 2 diabetes, a significantly (P = 0.0019) lower prevalence of haplogroup N9b was detected in subjects with myocardial infarction than in the controls. Especially, the prevalence of this haplogroup was significantly lower (P = 0.0007) in the male subjects with the disease than in the male controls. In contrast, there were trends towards higher prevalence of the disease in haplogroup G1 for males (P < 0.05). No significant haplogroup-related associations were detected for females. Our data suggest that haplogroup N9b confers resistance against myocardial infarction in Japanese males.

Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: a 1-year randomized placebo-controlled trial.

UNLABELLED: The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward's triangle regions. INTRODUCTION: The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals. In this study, we determined the effects of isoflavone intake, walking exercise, and their interaction on bone, fat mass, and lipid metabolism over 1 year in postmenopausal Japanese women. MATERIALS AND METHODS: A total of 136 postmenopausal women at <5 years after the onset of menopause were randomly assigned to four groups: (1) placebo, (2) walking (45 minutes/day, 3 days/week) with placebo, (3) isoflavone intake (75 mg of isoflavone conjugates/day), and (4) combination of isoflavone plus walking. BMD, fat mass, serum lipid, and serum and urinary isoflavone concentrations were assessed. RESULTS: A significant main effect of isoflavone on the reduction in trunk fat mass was obtained at 12 months. Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3, 6, and 12 months and that in the legs and arms at 6 and 12 months. Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention. After 12 months, a significant main effect of isoflavone on BMD was observed only at Ward's triangle. Walking prevented bone loss at the total hip and the Ward's triangle to significant degrees. The effect of the combined intervention on BMD at total hip and Ward's triangle regions was greater than that of either alone. No significant interaction was observed between isoflavone and walking in any measurements recorded during the study. CONCLUSIONS: Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward's triangle regions than either alone. Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners. Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women.