Genotype Score for Iron Status Is Associated with Muscle Fiber Composition in Women.
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ABSTRACT:
SUBMITTER: Takaragawa M
PROVIDER: S-EPMC8775127 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms have been associated with endurance athlete status, endurance performance phenotypes, and certain health-related markers of different pathologies such as metabolic syndrome, diabetes, and dyslipidemia. We hypothesized that they could be considered interesting candidates for explaining inter-individual variations in muscle fiber composition in humans. We aimed to examine possible associations of these polymorphisms with myosin heavy-chain (MHC) isoforms as markers of muscle fiber compositions in vastus lateralis muscle in a population of 214 healthy Japanese subjects, aged between 19 and 79 years. No significant associations were found in men for any measured variables. In contrast, in women, the PPARGC1A rs8192678 A/A genotype was significantly associated with a higher proportion of MHC-I (p = 0.042) and with a lower proportion of MHC-IIx (p = 0.033), and the NRF1 rs6949152 AA genotype was significantly associated with a higher proportion of MHC-I (p = 0.008) and with a lower proportion of MHC IIx (p = 0.035). In women, the genotype scores of the modes presenting the most significant results for PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms were significantly associated with MHC-I (p = 0.0007) and MHC IIx (p = 0.0016). That is, women with combined PPARGC1A A/A and NRF1 A/A genotypes presented the highest proportion of MHC-I and the lowest proportion of MHC-IIx, in contrast to women with combined PPARGC1A GG+GA and NRF1 AG+GG genotypes, who presented the lowest proportion of MHC-I and the highest proportion of MHC-IIx. Our results suggest possible associations between these polymorphisms (both individually and in combination) and the inter-individual variability observed in muscle fiber composition in women, but not in men.
| S-EPMC7563119 | biostudies-literature
Project description:Genetic polymorphisms and sex differences are suggested to affect muscle fiber composition; however, no study has investigated the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences. Therefore, the present study examined the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences in the Japanese population. The present study included 211 healthy Japanese individuals (102 men and 109 women). Muscle biopsies were obtained from the vastus lateralis to determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx). Moreover, we analyzed polymorphisms in α-actinin-3 gene ( ACTN3; rs1815739 ), angiotensin-converting enzyme gene ( ACE; rs4341 ), hypoxia-inducible factor 1 α gene ( rs11549465 ), vascular endothelial growth factor receptor 2 gene ( rs1870377 ), and angiotensin II receptor, type 2 gene ( rs11091046 ), by TaqMan single-nucleotide polymorphism genotyping assays. The proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%, respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID + DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE insertion/deletion (I/D) was significantly correlated with the proportion of MHC-I ( r = -0.23) and MHC-IIx ( r = 0.27) in men. In contrast, no significant correlation was observed between the examined polymorphisms and muscle fiber composition in women. These results suggest that the ACTN3 R577X and ACE I/D polymorphisms independently affect the proportion of human skeletal muscle fibers MHC-I and MHC-IIx in men but not in women. NEW & NOTEWORTHY In men, the RR + RX genotype of the α-actinin-3 gene ( ACTN3) R577X polymorphism was associated with a higher proportion of myosin heavy chain (MHC)-IIx. The ID + DD genotype of the angiotensin-converting enzyme gene ( ACE) insertion/deletion (I/D) polymorphism, in contrast to a previous finding, was associated with a higher proportion of MHC-I in men. In addition, the combined genotype of these polymorphisms was correlated with the proportion of MHC-I and MHC-IIx in men. Thus ACTN3 R577X and ACE I/D polymorphisms influence the muscle fiber composition in Japanese men.
| S-EPMC6008072 | biostudies-literature
Project description:This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04).
| S-EPMC3876997 | biostudies-literature
Project description:BackgroundAsthma and iron deficiency are common conditions. Whether iron status affects the risk of asthma is unclear.ObjectiveTo determine the relationship between iron status and asthma, lung function, and pulmonary inflammation.MethodsRelationships between measures of iron status (serum ferritin, serum soluble transferrin receptor (sTfR), and sTfR/log10ferritin (sTfR-F Index)) and asthma, lung function, and pulmonary inflammation were examined in women 20-49 years in the National Health and Nutrition Examination Survey. Logistic, linear, and quadratic regression models accounting for the survey design of NHANES were used to evaluate associations between iron status and asthma-related outcomes and were adjusted for race/ethnicity, age, smoking status, income, and BMI.ResultsApproximately 16% reported a lifetime history of asthma, 9% reported current asthma, and 5% reported a recent asthma episode/attack (n = 2906). Increased ferritin (iron stores) was associated with decreased odds of lifetime asthma, current asthma, and asthma attacks/episodes in the range of ferritin linearly correlated with iron stores (20-300ng/ml). The highest quintile of ferritin (>76 ng/ml) was also associated with a decreased odds of asthma. Ferritin levels were not associated with FEV1. Increased values of the sTfR-F Index and sTfR, indicating lower body iron and higher tissue iron need, respectively, were associated with decreased FEV1, but neither was associated with asthma. None of the iron indices were associated with FeNO.ConclusionIn US women, higher iron stores were inversely associated with asthma and lower body iron and higher tissue iron need were associated with lower lung function. Together, these findings suggest that iron status may play a role in asthma and lung function in US women.
| S-EPMC4331366 | biostudies-literature
Project description:The R577X polymorphism in the alpha-actinin-3 encoding gene (ACTN3) has been associated with elite athletic performance, and recently with differences in isometric and dynamic muscle strength and power in the general population. In this study we sought to determine the association of ACTN3 R577X genotype with muscle strength and mass phenotypes in men and women across the adult age span. Eight hundred forty-eight (n = 848) adult volunteers (454 men and 394 women) aged 22-90 yr were genotyped for ACTN3 R577X. Knee extensor (KE) shortening and lengthening peak torque values were determined using isokinetic dynamometry and fat-free mass (FFM) by dual-energy X-ray absorptiometry. Women deficient in alpha-actinin-3 (X/X; n = 53) displayed lower KE shortening peak torque (30 degrees /s: 89.5 +/- 3.5 vs. 99.3 +/- 1.4 N.m, P = 0.011; 180 degrees /s: 60.3 +/- 2.6 vs. 67.0 +/- 1.0 N.m, P = 0.019) and KE lengthening peak torque (30 degrees /s: 122.8 +/- 5.7 vs. 137.0 +/- 2.2 N.m, P = 0.022; 180 degrees /s: 121.8 +/- 5.8 vs. 138.5 +/- 2.2 N.m, P = 0.008) compared with R/X + R/R women (n = 341). Women X/X homozygotes also displayed lower levels of both total body FFM (38.9 +/- 0.5 vs. 40.1 +/- 0.2 kg, P = 0.040) and lower limb FFM (11.9 +/- 0.2 vs. 12.5 +/- 0.1 kg, P = 0.044) compared with R/X + R/R women. No genotype-related differences were observed in men. In conclusion, our results indicate that the absence of alpha-actinin-3 protein (i.e., ACTN3 X/X genotype) influences KE peak torque and FFM in women but not men.
| S-EPMC2584847 | biostudies-literature
Project description:Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10−5. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10−15) and with greater appendicular lean mass (p = 1.2 × 10−5), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.
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Project description:Total RNA-seq profiling of skeletal muscle.
2022-12-30 | GSE200398 | GEO
Project description:Perlecan is a component of the basement membrane that surrounds skeletal muscle. The aim of the present study is to identify the role of perlecan in skeletal muscle hypertrophy and myostatin signaling, with and without mechanical stress, using a mouse model (Hspg2(-/-)-Tg) deficient in skeletal muscle perlecan. We found that myosin heavy chain (MHC) type IIb fibers in the tibialis anterior (TA) muscle of Hspg2(-/-)-Tg mice had a significantly increased fiber cross-sectional area (CSA) compared to control (WT-Tg) mice. Hspg2(-/-)-Tg mice also had an increased number of type IIx fibers in the TA muscle. Myostatin and its type I receptor (ALK4) expression was substantially decreased in the Hspg2(-/-)-Tg TA muscle. Myostatin-induced Smad activation was also reduced in a culture of myotubes from the Hspg2(-/-)-Tg muscle, suggesting that myostatin expression and its signaling were decreased in the Hspg2(-/-)-Tg muscle. To examine the effects of mechanical overload or unload on fast and slow muscles in Hspg2(-/-)-Tg mice, we performed tenotomy of the plantaris (fast) muscle and the soleus (slow) muscle. Mechanical overload on the plantaris muscle of Hspg2(-/-)-Tg mice significantly increased wet weights compared to those of control mice, and unloaded plantaris muscles of Hspg2(-/-)-Tg mice caused less decrease in wet weights compared to those of control mice. The decrease in myostatin expression was significantly profound in the overloaded plantaris muscle of Hspg2(-/-)-Tg mice, compared with that of control mice. In contrast, overloading the soleus muscle caused no changes in either type of muscle. These results suggest that perlecan is critical for maintaining fast muscle mass and fiber composition, and for regulating myostatin signaling.
| S-EPMC2939214 | biostudies-literature
Project description:Heritability analysis of the microbiota has demonstrated the importance of host genotype in defining the human microbiota. The alpha (1,2)-fucosyltransferase 2 encoded by FUT2 is involved in the formation of the H antigen and the SNP, rs601338 is associated with ABO histo-blood group antigen secretion in the intestinal mucosa. Previous studies have provided non replicated results for the association of this polymorphism with the composition and inferred function of intestinal microbiota. We aimed to assess this relationship in a large cohort of 1,190 healthy individuals. Genotyping was performed using the HumanCoreEXOME chip, microbial composition was addressed by 16S rRNA gene sequencing. Firmicutes, Bacteroidetes, and Actinobacteria were the dominant phyla in this cohort. Although we have sufficient power to detect significant associations of FUT2 genotype/ inferred phenotype with the microbiota, our data demonstrate that FUT2 genotype and secretor status is not associated with microbial alpha diversity, microbial composition or inferred microbial function after correction for multiple testing. Thus, FUT2 genotype and inferred phenotype are not associated with human fecal microbial composition and imputed function.
| S-EPMC6219652 | biostudies-literature
Project description:The rise in non-heme iron (NHI) concentration observed in skeletal muscle of aging rodents is thought to contribute to the development of sarcopenia. The source of the NHI has not been identified, nor have the physiological ramifications of elevated iron status in aged muscle been directly examined. Therefore, we assessed plantaris NHI and heme iron (HI) levels in addition to expression of proteins involved in iron uptake (transferrin receptor-1; TfR1), storage (ferritin), export (ferroportin; FPN), and regulation (iron regulatory protein-1 (IRP1) and -2 (IRP2)) of male F344xBN F1 rats (n=10/group) of various ages (8, 18, 28, 32, and 36 months) to further understand iron regulation in aging muscle. In a separate experiment, iron chelator (pyridoxal isonicotinoyl hydrazone; PIH) or vehicle was administered to male F344xBN F1 rats (n=8/group) beginning at 30 months of age to assess the impact on plantaris muscle mass and function at ~36 months of age. Principle findings revealed the increased NHI concentration in old age was consistent with concentrating effects of muscle atrophy and reduction in HI levels, with no change in the total iron content of the muscle. The greatest increase in muscle iron content occurred during the period of animal growth and was associated with downregulation of TfR1 and IRP2 expression. Ferritin upregulation did not occur until senescence and the protein remained undetectable during the period of muscle iron content elevation. Lastly, administration of PIH did not significantly (p>0.05) impact NHI or measures of muscle atrophy or contractile function. In summary, this study confirms that the elevated NHI concentration in old age is largely due to the loss in muscle mass. The increased muscle iron content during aging does not appear to associate with cytosolic ferritin storage, but the functional consequences of elevated iron status in old age remains to be determined.
| S-EPMC3812819 | biostudies-literature