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Open Access Open Badges Research article

The CAG repeat polymorphism in the Androgen receptor gene modifies the risk for hypospadias in Caucasians

Tatjana Adamovic1 and Agneta Nordenskjöld12

Author Affiliations

1 Department of Women's and Children's Health and Center of Molecular Medicine (CMM), Karolinska Institutet, SE-171 76, Stockholm, Sweden

2 Pediatric Surgery Clinic, Astrid Lindgren Children Hospital, Karolinska University Hospital, SE-171 76, Stockholm, Sweden

BMC Medical Genetics 2012, 13:109  doi:10.1186/1471-2350-13-109

Published: 20 November 2012



Hypospadias is a birth defect of the urethra in males, and a milder form of 46,XY disorder of sexual development (DSD). The disease is characterized by a ventrally placed urinary opening due to a premature fetal arrest of the urethra development. Moreover, the Androgen receptor (AR) gene has an essential role in the hormone-dependent stage of sexual development. In addition, longer AR polyglutamine repeat lengths encoded by CAG repeats are associated with lower transcriptional activity in vitro. In the present study, we aimed at investigating the role of the CAG repeat length in the AR gene in hypospadias cases as compared to the controls. Our study included 211 hypospadias and 208 controls of Caucasian origin.


We amplified the CAG repeat region with PCR, and calculated the difference in the mean CAG repeat length between the hypospadias and control group using the T-test for independent groups.


We detected a significant increase of the CAG repeat length in the hypospadias cases when compared to the controls (contrast estimate: 2.29, 95% Confidence Interval (1.73-2.84); p-value: 0.001). In addition, the odds ratios between the hypospadias and controls revealed that the hypospadias cases are two to 3 times as likely to have longer CAG repeats than a shorter length for each repeat length investigated.


We have investigated the largest number of hypospadias cases with regards to the CAG repeat length, and we provide evidence that a higher number of the CAG repeat sequence in the AR gene have a clear effect on the risk of hypospadias in Caucasians.

Hypospadias; Androgen receptor gene; CAG repeats