Association between MAPT polymorphism but not APOE promoter and elite rugby athlete status

INTRODUCTION: Incidence and outcomes of concussions have been hypothesised to be genetically influenced. The APOE Promoter G219T (rs405509) polymorphism has been associated with differential promoter activity and unfavourable outcomes after traumatic brain injury. The TT genotype is associated with a 3-fold greater risk of multiple concussions. The TT genotype of MAPT (rs10445337) has also been associated with poorer outcomes after concussion. Rugby has one of the highest incidences of concussion in sport, so it was hypothesised that APOE Promoter TT and MAPT TT genotypes would be less prevalent in elite rugby athletes because those genotypes, previously associated with increased risk, would be less compatible with achieving elite athlete status. METHODS: Participants were from the RugbyGene project, comprising elite Caucasian male rugby athletes (n = 528; mean (standard deviation) height 1.85 (0.07) m, mass 101 (14) kg, age 29 (7) yr), including 420 rugby union (RU) athletes that for some analyses were divided into forwards and backs and 108 rugby league (RL) athletes. Non-athletes were 592 Caucasian men and women (57% male, height 1.72 (0.10) m, mass 74 (14) kg, age 31 (7) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using χ2 and odds ratio (OR) statistics. RESULTS: All genotype data were in Hardy-Weinberg equilibrium. For MAPT (rs10445337), the risk genotype (TT) was underrepresented in rugby athletes (60%) compared to non-athletes (66%), CT more common in rugby athletes (34%) than non-athletes (29%) and little difference in CC genotype frequencies (χ2 = 7.092, P = 0.029; TT genotype frequency OR = 0.80, 95% confidence intervals (CI) = 0.62-1.02). There were no differences in MAPT (rs10445337) genotype frequencies between RU forwards and backs. For APOE Promoter G219T (rs405509), there were no differences in genotype frequencies between all athletes (RU and RL) and non-athletes (27% TT genotype in players and non-athletes), nor between RU forwards and backs. CONCLUSION: The MAPT (rs10445337) TT genotype is 6% less common in elite rugby athletes than non-athletes. Therefore, carrying at least one rs10445337 C allele appears to increase the probability of sustained career success in the high-risk concussion environment of elite rugby, perhaps via a greater ability to recover from concussions.Peer reviewe

Prevalence and association of single nucleotide polymorphisms with sarcopenia in older women depends on definition

© 2020, The Author(s). The prevalence of sarcopenia depends on the definition used. There are, however, consistent sarcopenic characteristics, including a low muscle mass and muscle strength. Few studies have investigated the relationship between sarcopenia and genotype. A cross-sectional study was conducted with 307 community-dwelling ≥60-year-old women in South Cheshire, UK. Handgrip strength was assessed with a handgrip dynamometer and skeletal muscle mass was estimated using bioelectrical impedance. DNA was extracted from saliva (∼38%) or blood (∼62%) and 24 single-nucleotide polymorphisms (SNPs) were genotyped. Three established sarcopenia definitions - %Skeletal Muscle Mass (%SMM), Skeletal Muscle Mass Index (SMI) and European Working Group on Sarcopenia in Older People (EWGSOP) - were used to assess sarcopenia prevalence. Binary logistic regression with age as covariate was used to identify SNPs associated with sarcopenia. The prevalence of sarcopenia was: %SMM 14.7%, SMI 60.6% and EWGSOP 1.3%. Four SNPs were associated with the %SMM and SMI definitions of sarcopenia; FTO rs9939609, ESR1 rs4870044, NOS3 rs1799983 and TRHR rs7832552. The first three were associated with the %SMM definition, and TRHR rs7832552 with the SMI definition, but none were common to both sarcopenia definitions. The gene variants associated with sarcopenia may help proper counselling and interventions to prevent individuals from developing sarcopenia

An Investigation into Genetic Associations with Musculoskeletal Soft Tissue Injuries in Elite Rugby – Preliminary Findings

Peer reviewe

Atomic excitation during recollision-free ultrafast multi-electron tunnel ionization

Modern intense ultrafast pulsed lasers generate an electric field of sufficient strength to permit tunnel ionization of the valence electrons in atoms. This process is usually treated as a rapid succession of isolated events, in which the states of the remaining electrons are neglected. Such electronic interactions are predicted to be weak, the exception being recollision excitation and ionization caused by linearly-polarized radiation. In contrast, it has recently been suggested that intense field ionization may be accompanied by a two-stage `shake-up' reaction. Here we report a unique combination of experimental techniques that enables us to accurately measure the tunnel ionization probability for argon exposed to 50 femtosecond laser pulses. Most significantly for the current study, this measurement is independent of the optical focal geometry, equivalent to a homogenous electric field. Furthermore, circularly-polarized radiation negates recollision. The present measurements indicate that tunnel ionization results in simultaneous excitation of one or more remaining electrons through shake-up. From an atomic physics standpoint, it may be possible to induce ionization from specific states, and will influence the development of coherent attosecond XUV radiation sources. Such pulses have vital scientific and economic potential in areas such as high-resolution imaging of in-vivo cells and nanoscale XUV lithography.Comment: 17 pages, 4 figures, original format as accepted by Nature Physic

Collisional and thermal ionization of sodium Rydberg atoms I. Experiment for nS and nD atoms with n=8-20

Collisional and thermal ionization of sodium nS and nD Rydberg atoms with n=8-20 has been studied. The experiments were performed using a two-step pulsed laser excitation in an effusive atomic beam at atom density of about 2 10^{10} cm^{-3}. Molecular and atomic ions from associative, Penning, and thermal ionization processes were detected. It has been found that the atomic ions were created mainly due to photoionization of Rydberg atoms by photons of blackbody radiation at the ambient temperature of 300K. Blackbody ionization rates and effective lifetimes of Rydberg states of interest were determined. The molecular ions were found to be from associative ionization in Na(nL)+Na(3S) collisions. Rate constants of associative ionization have been measured using an original method based on relative measurements of Na_{2}^{+} and Na^{+} ion signals.Comment: 23 pages, 10 figure

Sarcopenia, obesity, and sarcopenic obesity: Relationship with skeletal muscle phenotypes and single nucleotide polymorphisms

Obesity may aggravate the effects of sarcopenia on skeletal muscle structure and function in the elderly, but no study has attempted to identify the gene variants associated with sarcopenia in obese women. Therefore, the aims of the present study were to: (1) describe neuromuscular function in sarcopenic and non-sarcopenic women with or without obesity; (2) identify gene variants associated with sarcopenia in older obese women. In 307 Caucasian women (71 ± 6 years, 66.3 ± 11.3 kg), skeletal muscle mass was estimated using bioelectric impedance, and function was tested with a 30 s one-leg standing-balance test. Biceps brachii thickness and vastus lateralis cross-sectional area (VLACSA) were measured with B-mode ultrasonography. Handgrip strength, maximum voluntary contraction elbow flexion (MVCEF), and knee extension torque (MVCKE) were measured by dynamometry, and MVCKE/VLACSA was calculated. Genotyping was performed for 24 single-nucleotide polymorphisms (SNPs), selected based on their previous associations with muscle-related phenotypes. Based on sarcopenia and obesity thresholds, groups were classified as sarcopenic obese, non-sarcopenic obese, sarcopenic non-obese, or non-sarcopenic non-obese. A two-way analysis of covariance was used to assess the main effects of sarcopenia and obesity on muscle-related phenotypes and binary logistic regression was performed for each SNP to investigate associations with sarcopenia in obesity. There were no significant obesity * sarcopenic status interactions for any of the investigated muscle-related phenotypic parameters. Neither sarcopenia nor obesity had a significant effect on biceps brachii thickness, but sarcopenia was associated with lower VLACSA (p = 0.003). Obesity was associated with lower MVCEF (p = 0.032), MVCKE (p = 0.047), and MVCKE/VLACSA (p = 0.012) with no significant effect of sarcopenia. Adjusted for age and height, three SNPs (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) were associated with sarcopenia in obese participants. Sarcopenia was associated with a smaller muscle size, while obesity resulted in a lower muscle quality irrespective of sarcopenia. Three gene variants (ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) suspected to affect muscle function, homocysteine metabolism, or DNA methylation, respectively, were associated with sarcopenia in obese elderly women. Understanding the skeletal muscle features affected by sarcopenia and obesity, and identification of genes related to sarcopenia in obese women, may facilitate early detection of individuals at particular risk of sarcopenic obesity

Static one-leg standing balance test as a screening tool for low muscle mass in healthy elderly women

Background: Identification of simple screening tools for detecting lower skeletal muscle mass may be beneficial for planning effective interventions in the elderly. Aims: We aimed to (1) establish a threshold for one-leg standing balance test (OLST) time for low muscle mass, and (2) test the ability of that threshold to assess muscular impairments in a poor balance group. Methods: Eyes-open OLST (maximum duration 30 s) was performed with right and left legs in 291 women (age 71 ± 6 years). OLST time was calculated as the sum of the OLST time of right and left legs. Fat-free mass (FFM), skeletal muscle mass (SMM), fat mass, biceps brachii and vastus lateralis sizes; handgrip strength (HGS), elbow flexion maximum torque (MVC ) and knee extension maximum torque (MVC ) were measured. Muscle quality was calculated as MVC /FFM and physical activity was assessed by questionnaire. Low muscle mass was defined as SMM of 22.1%, a previously established threshold for pre-sarcopenia. Results: The OLST threshold time to detect low muscle mass was 55 s (sensitivity: 0.63; specificity: 0.60). The poor balance group (OLST < 55 s) had higher fat mass (3.0%, p < 0.001), larger VL thickness (5.1%, p = 0.016), and lower HGS (− 10.2%, p < 0.001), MVC (− 8.2%, p = 0.003), MVC (− 9.5%, p = 0.012), MVC /FFM (− 11.0%, p = 0.004) and physical activity (− 8.0%, p = 0.024) compared to the normal balance group. While after adjusting age, the differences exist for HGS, fat mass and VL thickness only. Discussion: An OLST threshold of 55 s calculated as the summed score from both legs discriminated pre-sarcopenic characteristics among active, community-dwelling older women with limited potential (sensitivity 0.63, specificity 0.60). Conclusion: OLST, which can be performed easily in community settings without the need for more complex muscle mass measurement, may help identify women at risk of developing sarcopenia. EF KE KE relative EF KE K

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB