Cholesteryl Ester Transfer Protein (CETP) Polymorphisms Affect mRNA Splicing, HDL Levels, and Sex-Dependent Cardiovascular Risk

Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels. Allelic CETP mRNA expression ratios in 56 human livers were strongly associated with several variants 2.5–7 kb upstream of the transcription start site (e.g., rs247616 p = 6.4×10−5, allele frequency 33%). In addition, a common alternatively spliced CETP isoform lacking exon 9 (Δ9), has been shown to prevent CETP secretion in a dominant-negative manner. The Δ 9 expression ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p = 6.8×10−10) and intron 8 polymorphism rs9930761-T>C (5.6×10−8) (in high linkage disequilibrium with allele frequencies 6–7%). rs9930761 changes a key splicing branch point nucleotide in intron 8, while rs5883 alters an exonic splicing enhancer sequence in exon 9

Pre-season body composition has minimal influence on in-season match availability, and match performance in female Australian Football League (AFLW) players.

This study examined the relationship between pre-season body composition, in-season match performance, and match availability in female players competing in the Australian Football League Women's (AFLW) competition. With the outlawing of body composition assessments as part of pre-draft player evaluations in the AFLW, this study seeks to examine whether this is justified. Twenty-two (n = 22) players had body composition assessed with dual-energy x-ray absorptiometry at the beginning of the 2021 AFLW pre-season (whole-body and regional fat mass and lean soft-tissue mass [LSTM]). In-season match availability and match performance data (Coaches Score [CS], Champion Data Player Rank, average disposals, disposal and kicking efficiency) were collected throughout the 2021 competition. Pearson correlations were performed to assess if associations existed between body composition and in-season match performance and availability. A median split was performed to divide players into higher and lower performing groups for match performance variables. Two-sample independent t-tests were then used to assess differences between groups. No body composition characteristics could differentiate between in-season match availability groups (100% availability vs. <100% availability) or higher and lower performing groups for all match performance variables. Total leg LSTM asymmetry shared a moderate negative association with CS. Body composition may not be important for determining in-season match availability and performance in female AFLW players. Thus, the repercussions following the removal of pre-draft body composition assessments across the league may not be as significant as is currently perceived. Other physiological, biomechanical, or performance qualities are more variable and may mask the effect of body composition in these players. AFLW practitioners should prioritize the development of other important attributes, such as aerobic fitness, muscular strength and power, and technical skill

Characterising lower-body musculoskeletal morphology and whole-body composition of elite female and male Australian Football players.

BACKGROUND: Physical demands and injury rates differ between elite female and male Australian Football (AF) players. To improve understanding of contributing physical factors to these differences, the purpose of this study was to investigate lower-body morphology and whole-body composition of elite footballers competing in the Australian Football League (AFL) and Australian Football League Women's (AFLW). METHODS: Lower-body morphology and whole-body composition of 23 AFL players and 23 AFLW players were assessed using peripheral Quantitative Computed Tomography and Dual-energy X-ray Absorptiometry at the beginning of pre-season. Differences between cohorts, with sub-analyses of kicking vs. support limbs, and experienced vs. inexperienced player status were assessed using two-sample independent t-tests. Magnitude of differences were assessed using Cohen's d effect sizes. RESULTS: AFL players had greater absolute (p < 0.001; ES = 3.28) and relative (p < 0.001; ES = 2.29) whole body lean soft-tissue mass, with less absolute (p = 0.004; ES = 0.91) and relative (p < 0.001; ES = 2.29) fat mass than AFLW players. For AFLW players, no significant differences existed between kicking and support limbs with few differences observed between experienced and inexperienced players. CONCLUSIONS: Greater emphasis on physical development in AFLW players may be required to enable increases in muscle mass and skeletal robustness, to ensure they can tolerate the loads of elite competition