The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50–85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case–control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene–environment interactions—in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically “extreme” population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully

Bone mineral density in high-level endurance runners: part B—genotype-dependent characteristics

Purpose: Inter-individual variability in bone mineral density (BMD) exists within and between endurance runners and non-athletes, probably in part due to differing genetic profiles. Certainty is lacking, however, regarding which genetic variants may contribute to BMD in endurance runners and if specific genotypes are sensitive to environmental factors, such as mechanical loading via training. Method: Ten single-nucleotide polymorphisms (SNPs) were identified from previous genome-wide and/or candidate gene association studies that have a functional effect on bone physiology. The aims of this study were to investigate (1) associations between genotype at those 10 SNPs and bone phenotypes in high-level endurance runners, and (2) interactions between genotype and athlete status on bone phenotypes. Results: Female runners with P2RX7 rs3751143 AA genotype had 4% higher total-body BMD and 5% higher leg BMD than AC + CC genotypes. Male runners with WNT16 rs3801387 AA genotype had 14% lower lumbar spine BMD than AA genotype non-athletes, whilst AG + GG genotype runners also had 5% higher leg BMD than AG + GG genotype non-athletes. Conclusion: We report novel associations between P2RX7 rs3751143 genotype and BMD in female runners, whilst differences in BMD between male runners and non-athletes with the same WNT16 rs3801387 genotype existed, highlighting a potential genetic interaction with factors common in endurance runners, such as high levels of mechanical loading. These findings contribute to our knowledge of the genetic associations with BMD and improve our understanding of why some runners have lower BMD than others

Associations of bone mineral density-related genes and marathon performance in elite European Caucasian marathon runners.

Bone mineral density (BMD) is a multi-factorial phenotype determined by factors such as physical activity, diet and a sizeable genetic component. Athletic populations tend to possess higher BMD than non-athletes due to a larger volume of exercise completed. Despite this, some endurance runners can possess low BMD and/or suffer stress fractures, which can have negative impacts on their health and performance. Therefore, we hypothesised that elite endurance runners would possess a genotype associated with enhanced BMD and a reduced risk of injury, resulting in less training interruption and greater potential success. The study compared the genotype and allele frequencies of 5 genetic variants associated with BMD (LRP5 rs3736228, TNFRSF11B rs4355801, VDR rs2228570, WNT16 rs3801387, AXIN1 rs9921222) in elite (men < 2 h 30 min, n = 110; women < 3 h 00 min, n = 98) and sub-elite (men 2 h 30 min – 2 h 45 min, n = 181; women 3 h 00 min – 3 h 15 min, n = 67) marathon runners with those of a non-athlete control population (n = 474). We also investigated whether marathon personal best time was associated with a more “advantageous” BMD genotype. Congruent with our hypothesis, the “risk” T allele for the AXIN1 rs9921222 polymorphism was 5% more frequent in the control group than in sub-elites (P = 0.030, χ2 = 4.69) but no further differences were observed for this variant (P ≥ 0.083, χ2 ≤ 4.98). WNT16 rs3801387 genotype frequency differed between athletes and controls (P = 0.002, χ2 = 12.02) and elites vs controls (P = 0.008, χ2 = 9.72), as did allele frequency. However, contrary to our hypothesis, it was the “risk” A allele that was ~5% more frequent in athletes than controls. Similarly, when combining data from all 5 variants, the athletes had a lower Total Genotype Score than controls (53.6 vs 65.7; P ≤ 0.001), again suggesting greater genetic susceptibility to bone injury in athletes. Personal best times were not associated with genotype in any comparison. These results suggest that high-level endurance runners do not benefit from genetic resistance to bone injury and a resulting ability to sustain large training volumes, contradicting our hypothesis. High-level endurance runners appear to be at a higher risk of bone injury from a genetic perspective, for as yet unexplained reasons, although large inter-individual differences in genetic risk exist

Five Year Incidence of Visual Field Loss in Adult Chinese. The Beijing Eye Study.

PURPOSE: To describe the cumulative 5 year incidence of visual field loss in adult Chinese in Greater Beijing. METHODS: The Beijing Eye Study 2006 included 3251 subjects (mean age 60.4±10.1 years) who had participated in the Beijing Eye Study 2001 and returned for re-examination. All participants underwent a comprehensive eye examination, including visual field test by frequency doubling threshold perimetry. An abnormal visual field was defined as reduced sensitivity in at least one test location. Incident visual field loss was defined as a change in visual field from normal at baseline to abnormal at follow-up. RESULTS: An incident visual field loss was detected in 273 eyes (4.3±0.5%)/235 subjects (7.3±0.5%). It was significantly associated with higher age (P = 0.001), higher intraocular pressure (P<0.001), and higher fasting blood glucose concentration (P = 0.019). Considering only eyes (n = 140) with a detected cause for visual field loss, the most frequent causes were cataract (68 (48.6%) eyes) followed by glaucoma (23 (16.4%) eyes), diabetic retinopathy (13 (9.3%) eyes), age-related macular degeneration (10 (7.1%) eyes), and myopic degenerative retinopathy (9 (6.4%) eyes). For 133 (48.7%) eyes with a visual field loss, the cause for the VFL remained unclear. CONCLUSIONS: The 5-year incidence of visual field loss was 4.3±0.5% per eye or 7.3±0.5% per subject. It increased significantly with age, intraocular pressure, and fasting blood glucose level. Major causes for the incidence of visual field loss were cataract, glaucoma and diabetic retinopathy

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa

Dutch guideline on total hip prosthesis

Contains fulltext : 97840.pdf (publisher's version ) (Open Access

‘‘Beet-ing’’ the Mountain: A Review of the Physiological and Performance Effects of Dietary Nitrate Supplementation at Simulated and Terrestrial Altitude

Exposure to altitude results in multiple physiological consequences. These include, but are not limited to, a reduced maximal oxygen consumption, drop in arterial oxygen saturation, and increase in muscle metabolic perturbations at a fixed sub-maximal work rate. Exercise capacity during fixed work rate or incremental exercise and time-trial performance are also impaired at altitude relative to sea-level. Recently, dietary nitrate (NO3-) supplementation has attracted considerable interest as a nutritional aid during altitude exposure. In this review, we summarise and critically evaluate the physiological and performance effects of dietary NO3- supplementation during exposure to simulated and terrestrial altitude. Previous investigations at simulated altitude indicate that NO3- supplementation may reduce the oxygen cost of exercise, elevate arterial and tissue oxygen saturation, improve muscle metabolic function, and enhance exercise capacity/ performance. Conversely, current evidence suggests that NO3- supplementation does not augment the training response at simulated altitude. Few studies have evaluated the effects of NO3- at terrestrial altitude. Current evidence indicates potential improvements in endothelial function at terrestrial altitude following NO3- supplementation. No effects of NO3- supplementation have been observed on oxygen consumption or arterial oxygen saturation at terrestrial altitude, although further research is warranted. Limitations of the present body of literature are discussed, and directions for future research are provided

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases