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Association of Long Polyglycine Tracts (GGN Repeats) in Exon 1 of the Androgen Receptor Gene With Cryptorchidism and Penile Hypospadias in Iranian Patients

RAMIN RADPOUR^*,

MINA REZAEE^,

ALI TAVASOLY

SANAZ SOLATI

AHMAD SALEKI

From the ^* Department of Reproductive Genetics, Reproductive Biomedicine Research Center of Royan Institute, Tehran, Iran; the Genetic Research Center of Social Welfare and Rehabilitation Sciences University, Tehran, Iran; the Department of Nanotechnology, Avesina Research Institute, Beheshti University, Tehran, Iran; and the Department of Urology, Biomedical Research Center of Military University of Medical Sciences, Tehran, Iran.

Correspondence to: Ramin Radpour, Department of Reproductive Genetics, Reproductive Biomedicine Research Center of Royan Institute, PO Box 19395-4644, Tehran, Iran (e-mail: rradpour{at}royaninstitute.org).

Hypospadias (a urethral orifice located along the ventral side of the penis) and cryptorchidism (failure of the testes to descend into the scrotal sacs) are the 2 most common congenital malformations in males, affecting 0.3%–0.7% and 2%–4%, respectively, at birth. To study the association of CAG/GGN trinucleotide repeats in the androgen receptor gene with cryptorchidism and hypospadias in an Iranian population, we performed a case-control study of 76 cryptorchid and 92 hypospadiac (divided into subgroups of glanular, penile, and penoscrotal hypospadias) Iranian males. The length of the CAG/GGN repeat segment was evaluated by using polymerase chain reaction (PCR) sequencing in exon 1 and PCR–single-strand conformation polymorphism (PCR-SSCP) in exons 2–8. There were no significant differences in CAG lengths between the cases and controls, but GGN numbers were found to be significantly higher (median, 24 vs 22) among both subjects with penile hypospadias (P = .018) and those with a history of cryptorchidism (P = .001) compared with controls. In addition, the GGN numbers among subjects with penile hypospadias were significantly different compared with the 2 other subgroups of hypospadias (P = .001). We were able to identify 12 different CAG alleles and 8 different GGN alleles in the cryptorchid group. Although further studies are needed to elucidate the possible role of specific CAG/GGC combinations as a susceptible factor, our data suggested the possible association between polyglycin tract polymorphism in androgen receptor gene and cryptorchidism.

     Key words: CAG repeats, testicular dysgenesis syndrome, molecular diagnosis

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