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Background  Replication studies are essential for identifying credible associations between alleles and phenotypes. Validation of genotype-phenotype associations in the sports and exercise field is rare. An initial genetic association study suggested that rs1049305 (C > G) in the 3′ untranslated region (3′UTR) of the aquaporin-1 (AQP1) gene was associated with marathon running (MR) performance level in Hispanic males. To validate this finding, we conducted a replication analysis in an independent case-control sample of Hispanic male marathon runners ( n  = 1430; cases  n  = 713 and controls  n  = 717). A meta-analysis was utilized to test the extent of the association between the initial results and the present report. It also provided to test the heterogeneity (variation) between the two studies.    Results  The replication study showed a statistically significant ( p  ≤ 0.05) association between rs1049305 (C > G) of the AQP1 gene and MR performance level. Association test results using a fixed effect model for the combined, original study and the present report, yielded an odds ratio = 1.28, 95% confidence interval = 1.13–1.45,  p  = 0.0001. The extent of the measures of heterogeneity was Tau-squared = 0,  H  statistic = 1,  I  2  statistic = 0, and Cochran’s  Q  test ( Q  = 0.29;  p  value 0.59), indicated the variation between studies were due to chance and not to differences in heterogeneity between the two studies. Within the limitations of the present replication, contrast of two studies and its effects on meta-analysis, the findings were robust.    Conclusion  This study successfully replicated the results of Martínez et al. (Med Sportiva 13:251-5, 2009). The meta-analysis provided further epidemiological credibility for the hypothesis of association between the DNA rs1049305 (C > G) variation in the 3′UTR of the AQP1 gene and MR running performance level in Hispanics male marathon runners. It is not precluded that a linked DNA structure in the surrounding molecular neighborhood could be of influence by been part of the overly complex phenotype of MR performance level.

The Association of Aquaporin-1 Gene with Marathon Running Performance Level: a Confirmatory Study Conducted in Male Hispanic Marathon Runners