title: Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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-1beta gene (IL-1B) at -511 and +3954 positions, and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (IL-1RN) were assessed.
  
  
  RESULTS
  We found a 2-fold higher frequency of the IL-1RN 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 IL-1RN 2/2 genotype did not differ between groups. No significant differences between athletes and controls were found for either -511 or +3954 IL-1B 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 IL-1RN 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%).
  
  
  CONCLUSIONS
  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 IL-1RN polymorphism may have implications for muscle health, performance, and/or recovery capacities. Further studies are needed to assess these specific issues. As VNTR IL-1RN 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.
authors.affiliation: Department of Biomedical Sciences and Technologies, School of Medicine, Università di Udine, Udine, Italy. sabina.cauci@uniud.it
authors.forename: Sabina
authors.initials: S
authors.lastname: Cauci
authors.forename: Manuela
authors.initials: M
authors.lastname: Di Santolo
authors.forename: Kelli K
authors.initials: KK
authors.lastname: Ryckman
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Banfi
mesh_terms: D000328:Adult; D000483:Alleles; D056352:Athletes; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D007438:Introns; D008297:Male; D018598:Minisatellite Repeats; D018482:Muscle, Skeletal / Q000378:metabolism; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta