Remarkably low incidence of hypospadias in Greenland despite high exposure to endocrine disrupters; possible protective effect of androgen receptor genotype.

Endocrine disrupters, such as persistent organohalogen pollutants (POPs) may cause hypospadias, which is a common congenital anomaly in males, affecting 0.2-0.7%. We hypothesized that hypospadias incidence would be high among Greenlanders, who are one of the most POP exposed populations on earth through consumption of contaminated sea mammals. Interestingly, among the 11 076 boys born in Greenland 1982-2002, only two cases of hypospadias were noted (incidence 0.02%; 95% CI: 0.002-0.06). Normal male sexual differentiation is dependent on the androgen receptor (AR). AR function is regulated by polymorphic repeats of CAG and GGN trinucleotide bases. In Greenland 85% were carriers of GGN=23, which in a previous report was less frequent in patients with hypospadias than in the general population. This finding indicates that AR genotype could contribute to a genetic predisposition in Greenlanders, who despite one of the worlds highest body burden of POPs, seem to be protected from hypospadias.