Genetic polymorphisms of ESR1 and ESR2 that may influence estrogen activity and the risk of hypospadias.
BACKGROUND
The etiology of hypospadias is regarded as a complex disorder with both genetic and environmental contributions. Although alterations in androgen activity have been associated with hypospadias, few associations with estrogen activity have been documented. Here, we assessed genetic polymorphisms in estrogen receptor genes and their association with hypospadias.


METHODS
Using a case-control study of 59 cases with hypospadias and 286 controls, we examined the association of hypospadias with the following polymorphisms: PvuII and XbaI in ESR1, and 2681-4A>G in ESR2.


RESULTS
For the cases, we found a negative association with the G allele containing variants of ESR1 XbaI (OR = 0.52, P < 0.05), and a negative association with the G allele containing variants of ESR2 2681-4A>G (OR = 0.59, P < 0.05). For the cases, we also identified a negative association with the CG haplotype, and a positive association with the CA haplotype, defined by ESR1 PvuII and XbaI (P < 0.05).


CONCLUSIONS
These findings suggest that the G allele containing variants of ESR1 XbaI and the G allele containing variants of ESR2 2681-4A>G may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase its risk.
Ban
Susumu
S
Department of Public Health, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan. sban@med.hokudai.ac.jp
Sata
Fumihiro
F
Kurahashi
Norie
N
Kasai
Setsuko
S
Moriya
Kimihiko
K
Kakizaki
Hidehiro
H
Nonomura
Katsuya
K
Kishi
Reiko
R
D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D004967:Estrogens / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D007021:Hypospadias / Q000235:genetics*; D007564:Japan; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens