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

Association of MMP3 but not TIMP2 gene variants with elite rugby player status and rugby code

Introduction: Achilles tendon pathology and anterior cruciate ligament rupture are multifactorial conditions for which genetic risk factors have been identified. Single nucleotide polymorphisms (SNPs) within the MMP3 (rs591058, rs679620, rs650108) and TIMP2 (rs4789932) genes have previously been associated with tendon and ligament pathologies. Although not entirely clear, prior literature indicates the risk alleles for Achilles tendon pathology as T (rs591058), G (rs679620) and A (rs650108) for MMP3. However, prior evidence regarding TIMP2 is equivocal. MMP3 is considered an essential regulator of matrix degradation and remodelling within diseased and normal musculoskeletal soft tissues. TIMP2 maintains homeostasis in the extracellular matrix in part by inhibiting MMP function. Given the high incidence and severity of tendon and ligament injuries in elite rugby athletes, we hypothesised that the aforementioned SNPs would be associated with career success. Methods: Participants from the RugbyGene project were elite Caucasian male rugby athletes (n = 566; 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 120 rugby league (RL) athletes. Non-athletes were 589 Caucasian men and women (n = 589, 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: As hypothesized, the MMP3 rs591058 risk genotype (TT) was less frequent in rugby athletes (28%) compared to non-athletes (33%) (Χ2 = 7.265, P = 0.026; OR = 1.18, 95% confidence intervals (CI) = 0.86-1.63). No differences were found for MMP3 rs679620, rs650108 or TIMP2 rs4789932 between rugby athletes and non-athletes. When RL athletes were compared to non-athletes, the risk genotype (TT) of MMP3 rs591058 was underrepresented in RL athletes (19%) compared to non-athletes (33%). The MMP3 rs679620 ‘protective’ allele (C) was more frequent in RL athletes (55%) compared to non-athletes (48%) (OR = 1.3, 95% CI = 0.98-1.74). However, for MMP3 rs650108 the ‘risk’ allele (A) was overrepresented in RL athletes (32%) compared to non-athletes (26%). There were no genotype differences for any gene variant between RU athletes and non-athletes. The ‘risk’ allele (T) of the MMP3 rs679629 polymorphism and the ‘protective’ allele (G) of the MMP3 rs650108 polymorphism were less common in RL (45%, 68%, respectively) than RU athletes (54%, 76%, respectively). Conclusion: We provide evidence for elite rugby athletes possessing a protective genetic profile regarding tendon and ligament injury risk. Notably, a less frequent rs591058 TT genotype in athletes suggests a lower risk of injury could therefore enhance career success in rugby. Furthermore, RL players appear to have differing genetic characteristics compared to their RU counterparts, which might reflect some differences in physiological demands between codes.Peer reviewedFinal Published versio

Space-time clustering of Burkitt's lymphoma in the West Nile district of Uganda: 1961-1975.

Epidemiological data relating to all 202 patients diagnosed with Burkitt's Lymphoma (BL) in the West Nile District of Uganda in the period 1961 to 1975 have been reviewed and analysed. Statistically significant evidence of space-time clustering of cases, first reported for the period 1961-65, was also present during 1972-73, but not during other periods. The patients involved in such clusters were found to be older than other patients (P less than 0.001). The average annual incidence of BL in the District was 2.45 x 10(-5) and overall there was no change in the incidence during the study period. However, there were statistically significant changes in incidence in different counties, which could not be explained as case-ascertainment artifacts. One sib pair of patients with BL was found and the series also included 7 instances of BL in two cousins. It is suggested that study of variation in the intensity and type of malarial infestation in different areas at different times may help explain the epidemiological findings and suggest what, if any, aspects of this infection are critical for inducing BL

The genetic contribution to severe post-traumatic osteoarthritis

Objective: to compare the combined role of genetic variants loci associated with risk of knee or hip osteoarthritis (OA) in post-traumatic (PT) and non-traumatic (NT) cases of clinically severe OA leading to total joint replacement. Methods: A total of 1590 controls, 2168 total knee replacement (TKR) cases (33.2% PT) and 1567 total hip replacement (THR) cases (8.7% PT) from 2 UK cohorts were genotyped for 12 variants previously reported to be reproducibly associated with risk of knee or hip OA. A genetic risk score was generated and the association with PT and NT TKR and THR was assessed adjusting for covariates. Results: For THR, each additional genetic risk variant conferred lower risk among PT cases (OR=1.07, 95% CI 0.96 to 1.19; p=0.24) than NT cases (OR 1.11, 95% CI 1.06 to 1.17; p=1.55×10−5). In contrast, for TKR, each risk variant conferred slightly higher risk among PT cases (OR 1.12, 95% CI 1.07 to 1.19; p=1.82×10−5) than among NT cases (OR 1.08, 95% CI 1.03 to 1.1; p=0.00063). Conclusions: Based on the variants reported to date PT TKR cases have at least as high a genetic contribution as NT cases

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

Peer reviewe

Bone Mineral Density and Associated Genetic Variants in High-level Caucasian Marathon Runners

INTRODUCTION:Endurance runners (except those who may have low energy availability) tend to have higher total and/or loading site-specific bone mineral density (BMD) in comparison with non-athletes, most likely due to the larger volume of exercise completed. A large genetic component also contributes to BMD, although little is known about which specific genes are involved, whether particular genotypes are sensitive to mechanical loading and the impact of such an interaction on BMD. This study investigated if high-level endurance runners possess enhanced BMD associated with an “advantageous” genetic predisposition, via a potential gene-physical activity interaction.METHODS:Age- and weight-adjusted total BMD (TBMD) and leg BMD (LBMD) measured via Dual-energy X-ray absorptiometry of 67 high-level Caucasian marathon runners (males < 2 h 45 min, n = 37; females < 3 15 min, n = 30) was compared with 40 male and 26 female non-athletes. LRP5 rs3736228, TNFRSF11B rs4355801, VDR rs2228570, WNT16 rs3801387 and AXIN1 rs9921222 variants were then investigated singularly, and collectively, as a total genotype score (TGS) via multivariate analysis of variance in a subgroup of this cohort (male runners n = 19, controls n = 26; female runners n = 17, controls n = 14). RESULTS:Male runners had higher TBMD (1.34 vs 1.28 g/cm2; P=0.02) and LBMD (1.53 vs 1.42 g/cm2; P=<0.01) than non-athletes. Female runners had higher LBMD than non-athletes (1.30 vs 1.22 g/cm2; P=0.02) but not TBMD (1.23 vs 1.18 g/cm2; P=0.22). An interaction (P=0.047) was observed between VDR rs2228570 genotype and group regarding LBMD in males: ff genotype runners had 0.02 g/cm2 higher LBMD than FF or Ff runners, but the FF genotype had the highest LBMD (1.45 g/cm2) amongst non-athletes. LBMD was also 0.12 g/cm2 higher in ff runners compared to ff non-athletes, whereas FF and Ff runners had 0.09 g/cm2 higher LBMD compared to their genotype-matched controls. No other interactions or variants, individually or collectively as part of a TGS, were associated with BMD (P≥0.11). CONCLUSION:High-level female runners possess higher LBMD but not TBMD in comparison with non-athletes whereas male runners possess both higher TBMD and LBMD than non-athletes. Consistent with prior literature, we observed higher BMD in VDR rs2228570 FF genotype in non-athletes, which may be due to increased biological activity associated with the F variant. However, our preliminary data suggest that the ff genotype may be associated with enhanced LBMD in male runners via a gene-environment interaction.Peer reviewedFinal Published versio

“I’d rather wait and see what’s around the corner”: a multi-perspective qualitative study of treatment escalation planning in frailty

Introduction People living with frailty risk adverse outcomes following even minor illnesses. Admission to hospital or the intensive care unit is associated with potentially burdensome interventions and poor outcomes. Decision-making during an emergency is fraught with complexity and potential for conflict between patients, carers and clinicians. Advance care planning is a process of shared decision-making which aims to ensure patients are treated in line with their wishes. However, planning for future care is challenging and those living with frailty are rarely given the opportunity to discuss their preferences. The aim of the ProsPECT (Prospective Planning for Escalation of Care and Treatment) study was to explore perspectives on planning for treatment escalation in the context of frailty. We spoke to people living with frailty, their carers and clinicians across primary and secondary care. Methods In-depth online or telephone interviews and online focus groups. The topic guide explored frailty, acute decision-making and planning for the future. Data were thematically analysed using the Framework Method. Preliminary findings were presented to a sample of study participants for feedback in two online workshops. Results We spoke to 44 participants (9 patients, 11 carers and 24 clinicians). Four main themes were identified: frailty is absent from treatment escalation discussions, planning for an uncertain future, escalation in an acute crisis is ‘the path of least resistance’, and approaches to facilitating treatment escalation planning in frailty. Conclusion Barriers to treatment escalation planning include a lack of shared understanding of frailty and uncertainty about the future. Emergency decision-making is focussed on survival or risk aversion and patient preferences are rarely considered. To improve planning discussions, we recommend frailty training for non-specialist clinicians, multi-disciplinary support, collaborative working between patients, carers and clinicians as well as broader public engagement

Teacher resilience in adverse contexts: issues of professionalism and professional identity

Teacher resilience is a construct that is relative, developmental and dynamic; it is socially constructed and depends on personal and professional dispositions. Issues of commitment, professionalism, and professional identity, for instance, need to be taken into account if teacher resilience is to be fully understood. In this chapter I draw upon a larger piece of research aimed at investigating teachers’ work and lives in challenging circumstances. Data were collected through a national survey (n=2702 teachers), focus group (n=99 teachers) and interviews to 11 school principals. Findings suggest the connection between teacher commitment and resilience which are associated with issues of school culture and leadership, a sense of vocation, and teachers’ beliefs and professional values. Factors and sources of teacher motivation and resilience are also identified within a context marked by teacher intensification, lack of trust, worsening of teaching conditions, lower social and economic status and legislative “tsunami”. The chapter ends with the discussion of the importance of relationships in the teaching profession and issues of motivation and professionalism which entails given ways of being and feeling as a teacher.Financial Support by CIEC (Research Centre on Child Studies, IE, UMinho; FCT R&D unit 317, Portugal) by the Strategic Project UID/CED/00317/2013, with financial support of National Funds through the FCT (Foundation for Science and Technology) and co-financed by European Regional Development Funds (FEDER) through the COMPETE 2020 - Competitiveness and Internationalization Operational Program (POCI) with the reference POCI-01-0145-FEDER-00756

Anthropometric and Physiological Characteristics of Elite Male Rugby Athletes

This is the first article to review the anthropometric and physiological characteristics required for elite rugby performance within both Rugby Union (RU) and Rugby League (RL). Anthropometric characteristics such as height and mass, and physiological characteristics such as speed and muscular strength, have previously been advocated as key discriminators of playing level within rugby. This review aimed to identify the key anthropometric and physiological properties required for elite performance in rugby, distinguishing between RU and RL, forwards and backs and competitive levels. There are differences between competitive standards such that, at the elite level, athletes are heaviest (RU forwards ~111 kg, backs ~93 kg; RL forwards ~103 kg, backs ~90 kg) with lowest % body fat (RU forwards ~15%, backs ~12%; RL forwards ~14%, backs ~11%), they have most fat-free mass and are strongest (Back squat: RU forwards ~176 kg, backs ~157 kg; RL forwards ~188 kg, backs ~ 168 kg; Bench press: RU forwards ~131 kg, backs ~118 kg; RL forwards ~122 kg, backs ~113 kg) and fastest (10 m: RU forwards ~1.87 s, backs ~1.77 s; 10 m RL forwards ~1.9 s, backs ~1.83 s). We also have unpublished data that indicate contemporary RU athletes have less body fat and are stronger and faster than the published data suggest. Regardless, well-developed speed, agility, lower-body power and strength characteristics are vital for elite performance, probably reflect both environmental (training, diet, etc.) and genetic factors, distinguish between competitive levels and are therefore important determinants of elite status in rugby.Published versio