부산대학교 도서관

Context: Mutations in the androgen receptor (AR) gene might be associated with infertility mainly because they cause various degrees of androgen insensitivity. Objective: The aim of the study was to evaluate the frequency and type of AR variants in a large cohort of infertile males. Methods: A total of 8224 males of Italian idiopathic infertile couples were referred to the University Hospital of Padova. The main outcome measures were mutational screening of AR, computational, and functional analyses. Results: We found 131 patients (1.6%) harboring 45 variants in AR gene, of which 18 were novel missense AR variants. Patients with AR gene variants had lower sperm count (P = .048), higher testosterone (T) concentration (P< .0001), and higher androgen sensitivity index (ASI) (luteinizing hormone * T, P< .001) than patients without variants. Statistical analyses found T [greater than or equal to] 15.38 nmol/L and ASI [greater than or equal to] 180 IU * nmol/[L.sup.2] as the threshold values to discriminate with good accuracy patients with AR variants. Patients with oligozoospermia and T [greater than or equal to] 15.38 nmol/L had a 9-fold increased risk of harboring mutations compared with patients with normal sperm count and T < 15.38 nmol/L (odds ratio 9.29, 95% CI 5.07-17.02). Using computational and functional approaches, we identified 2 novel variants, L595P and L791I, as potentially pathogenic. Conclusion: This is the largest study screening AR gene variants in men of idiopathic infertile couples. We found that the prevalence of variants increased to 3.4% in oligozoospermic subjects with T [greater than or equal to] 15.38 nmol/L. Conversely, more than 80% of men with AR gene variants had low sperm count and high T levels. Based on our findings, we suggest AR sequencing as a routine genetic test in cases of idiopathic oligozoospermia with T [greater than or equal to] 15.38 nmol/L. Key Words: androgen insensitivity, androgen receptor, infertility, oligozoospermia, testosterone
Male factor infertility is a multifactorial disorder responsible, alone or in combination with female factors, for about 50% of cases of couple infertility (1, 2). Genetic factors are involved in [...]