Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status

<p>Abstract</p> <p>Background</p> <p>The interleukin-1 (IL-1) family of cytokines is involved in the inflammatory and repair reactions of skeletal muscle during and after exercise. Specifically, plasma levels of the IL-1 receptor antagonist (IL-1ra) increase dramatically after intense exercise, and accumulating evidence points to an effect of genetic polymorphisms on athletic phenotypes. Therefore, the IL-1 family cytokine genes are plausible candidate genes for athleticism. We explored whether IL-1 polymorphisms are associated with athlete status in European subjects.</p> <p>Methods</p> <p>Genomic DNA was obtained from 205 (53 professional and 152 competitive non-professional) Italian athletes and 458 non-athlete controls. Two diallelic polymorphisms in the IL-1β gene (<it>IL-1B</it>) at -511 and +3954 positions, and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (<it>IL-1RN</it>) were assessed.</p> <p>Results</p> <p>We found a 2-fold higher frequency of the <it>IL-1RN </it>1/2 genotype in athletes compared to non-athlete controls (OR = 1.93, 95% CI = 1.37-2.74, 41.0% vs. 26.4%), and a lower frequency of the 1/1 genotype (OR = 0.55, 95% CI = 0.40-0.77, 43.9% vs. 58.5%). Frequency of the <it>IL-1RN </it>2/2 genotype did not differ between groups. No significant differences between athletes and controls were found for either -511 or +3954 <it>IL-1B </it>polymorphisms. However, the haplotype (-511)C-(+3954)T-(VNTR)2 was 3-fold more frequent in athletes than in non-athletes (OR = 3.02, 95% CI = 1.16-7.87). Interestingly, the <it>IL-1RN </it>1/2 genotype was more frequent in professional than in non-professional athletes (OR = 1.92, 95% CI = 1.02-3.61, 52.8% vs. 36.8%).</p> <p>Conclusions</p> <p>Our study found that variants at the IL-1ra gene associate with athletic status. This confirms the crucial role that cytokine IL-1ra plays in human physical exercise. The VNTR <it>IL-1RN </it>polymorphism may have implications for muscle health, performance, and/or recovery capacities. Further studies are needed to assess these specific issues. As VNTR <it>IL-1RN </it>polymorphism is implicated in several disease conditions, athlete status may constitute a confounding variable that will need to be accounted for when examining associations of this polymorphism with disease risk.</p

Climate ambition and respective capabilities: are England’s local emissions targets spatially just?

To date, 79% of Local Authorities (LAs) in England have a climate plan to reduce their greenhouse gas emissions by 2050 or sooner. Yet questions remain over the collective impact of these plans and targets in terms of their contribution to a national net zero carbon budget given that the LA targets are voluntary and largely uncoordinated. There is therefore scope to explore if and how the LA target-setting process could be improved. We evaluate regional ambition in the emissions targets of 311 English LAs. We assess whether the subnational targets are aligned with a national net zero carbon budget and whether LAs take proportionate action based on their respective capabilities. It is also unclear whether LAs have the resources to implement the often highly ambitious targets they have committed to. Using a composite indicator approach, we assess the relative capability of different LAs to decarbonize, as well as the degree of ambition they are demonstrating. We find that many LAs are not taking as much action as other LAs that may have less capability to act. This suggests that burden-sharing between regions and LAs is inequitable. We offer a series of policy recommendations to improve the fairness and effectiveness of the LA target-setting process as a climate governance mechanism, including establishing a statutory target-setting requirement with appropriate resourcing, and introducing a national net zero indicator framework to monitor progress. This framework could be used in England, or in other countries, to assess progress. It would also allow funding and resources to be better directed to regions and LAs that require more support to reach net zero emission targets, rendering the transition more ‘spatially just’ and enabling its delivery