The effect of human genetic variability on basal values of serum and urine biomarkers: implications in anti‐doping analysis

Abstract

The inter‐individual variability, due to genetic polymorphisms, can significantly affect the levels of specific target analytes that are measured in the antidoping field as diagnostic biomarkers of the recourse to prohibited substances and methods. This variability could affect the reliability of the test, increasing the risk of both “false‐negative” and “false‐positive”results. In this work we are assessing whether, and if so, to what extent, some selected human genetic polymorphisms can affect the results of both direct and indirect doping analyses, with particular reference to those markers for which threshold values are fixed, therefore imposing their quantitative determination. In the field of anti‐doping research, the presence of polymorphisms involves a series of questions regarding the genetic influence on the susceptibility to both screening and confirmation analyses of prohibited substances. We have pre‐selected Single Nucleotide Polymorphisms (SNP) and Copy Number Variation (CNV) of genes of particular interest in anti‐doping: DNA was extracted from both urinary and blood matrix. The results of the individual genotyping have been utilized in order to determine the correlation with the basal values of specific biomarkers. Specifically, we have considered the CNV polymorphism of UGT2B17 and the SNP of UGT2B15, both of relevance for the levels of endogenous anabolic androgenic steroids; and the SNP rs1520220, rs6873545 and rs7703713, of relevance for the detection of doping by human growth hormone and insulin growth factor 1. Our results show that genetic variability may impact on the reliability of anti‐doping tests especially in the case of biomarkers for which population‐based threshold are in force to discriminate a negative result and an adverse analytical finding.