Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Children's Hospital Los Angeles, 1441 Eastlake Avenue, MC-9175, Los Angeles, California 90033, USA.
J Clin Endocrinol Metab. 2012 Mar;97(3):E393-9. doi: 10.1210/jc.2011-2439. Epub 2011 Dec 21.
Cryptorchidism is the most frequent congenital malformation among males, the major established risk factor for testicular germ cell tumors, and a presumed infertility risk factor. Androgens are essential for testicular descent, and functional genetic polymorphisms in the androgen receptor gene (AR) are postulated to influence cryptorchidism risk.
The aim of the study was to investigate whether the CAG repeat length polymorphism in exon 1 of the AR is associated with cryptorchidism risk.
We conducted a family-based genotype-risk association study employing the transmission disequilibrium test for genotypic variants transmitted on the X-chromosome at a university-affiliated regional children's hospital.
We studied 127 Hispanic boys with persistent cryptorchidism and comorbidities described in detail and their biological mothers.
Genotypes defined by number of CAG repeats were measured for each member of participating son-mother pairs.
Associations between CAG tract length genotype and cryptorchidism risk were estimated using matched-pairs logistic regression.
Cryptorchidism risk was significantly associated with shorter CAG repeats [CAG≤19 vs. CAG≥20, odds ratio (OR)=0.44; 95% confidence interval (CI), 0.23-0.88]. This association was restricted to cryptorchidism with accompanying comorbidities, which was primarily hernia [CAG≤19 vs. CAG≥20, OR=0.35 (95% CI, 0.16-0.78)], and was strongest for bilateral cryptorchidism [CAG≤19 vs. CAG≥20, OR=0.09 (95% CI, 0.010-0.78)].
Androgen receptor genotypes encoding moderate functional variation may influence cryptorchidism risk, particularly among boys with bilateral nondescent or congenital hernia, and may explain in part the elevated risk of testicular seminoma experienced by ex-cryptorchid boys. Mechanistic research is warranted to examine both classical and nonclassical mechanisms through which androgens may influence risk of cryptorchidism and related conditions.
隐睾症是男性中最常见的先天性畸形，是睾丸生殖细胞肿瘤的主要既定风险因素，也是假定的不育风险因素。雄激素对睾丸下降至关重要，雄激素受体基因（AR）中的功能性遗传多态性被认为会影响隐睾症的风险。
本研究旨在探讨 AR 外显子 1 中的 CAG 重复长度多态性是否与隐睾症风险相关。
我们在一所附属大学附属的地区儿童医院进行了一项基于家族的基因型风险关联研究，采用传递不平衡检验分析 X 染色体上的基因型变异。
我们研究了 127 名患有持续性隐睾症和详细描述的合并症的西班牙裔男孩及其生物学母亲。
为参与母子对的每个成员测量 CAG 重复次数定义的基因型。
使用配对病例对照逻辑回归估计 CAG 片段长度基因型与隐睾症风险之间的关联。
隐睾症风险与较短的 CAG 重复明显相关[CAG≤19 与 CAG≥20，优势比（OR）=0.44；95%置信区间（CI），0.23-0.88]。这种关联仅限于伴有合并症的隐睾症，主要是疝[CAG≤19 与 CAG≥20，OR=0.35（95% CI，0.16-0.78)]，双侧隐睾症最强[CAG≤19 与 CAG≥20，OR=0.09（95% CI，0.010-0.78)]。
编码中度功能变异的雄激素受体基因型可能会影响隐睾症的风险，特别是对于双侧未降或先天性疝的男孩，并且可能部分解释了曾经的隐睾症男孩睾丸精原细胞瘤风险升高的原因。有必要进行机制研究，以检查雄激素可能通过经典和非经典机制影响隐睾症和相关疾病风险的机制。
