The opposite behaviors in terms of clinical expressivity detected for CAPN-UCSNP44 and TNFR2-M196R rare variants suggest these variants to be sensitizing and protective factors respectively in adrenal hyperandrogenism.
In conclusion, the M196R (676 T-->G) variant in exon 6 of TNFRSF1B is associated with hyperandrogenism and PCOS, further suggesting a role for inflammatory cytokines in the pathogenesis of these disorders.