Deletion in the uridine diphosphate glucuronyltransferase 2B17 gene is associated with delayed pubarche in healthy boys.
Deletion in the uridine diphosphate glucuronyltransferase 2B17 gene is associated with delayed pubarche in healthy boys.
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DOI：
10.1530/ec-18-0080
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发表时间：
2018-03
影响因子：
2.9
通讯作者：
Juul A
中科院分区：
文献类型：
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作者：
Mouritsen A;Busch AS;Aksglaede L;Rajpert-De Meyts E;Juul A
只有少数基因位点已知与男性青春期事件有关。在尿液中排泄睾酮（T）和其他类固醇的能力取决于硫酸化和葡萄糖醛酸化。几种必需的葡萄糖醛酸苷酶之一由UGT 2B 17基因编码。在一份初步报告中，我们发现男孩中UGT 2B 17纯合缺失与尿T排泄减少相关。我们假设葡萄糖醛酸化能力较低的男孩可能改变了雄激素的作用和排泄，影响阴毛初长，因为这代表了T依赖性事件。纳入了668名年龄为6.1-21.9岁的健康男孩（横断面）（2005年至2006年进行的COPENHAGEN青春期研究）。其中65名男孩每6个月进行一次纵向随访。对参与者进行UGT 2B 17拷贝数变异（CNV）基因分型。临床青春期分期包括测量身高、人体测量和血清生殖激素水平。668名男孩中有59名（8.8%）存在UGT 2B 17纯合缺失（del/del）。这些男孩的平均年龄为12.73岁（12.00-13.46），UGT 2B 17缺失杂合子（del/ins）男孩的平均年龄为12.40岁（12.11-12.68），野生型基因型（ins/ins）男孩的平均年龄为12.06岁（11.79-12.33）（P = 0.029，经BMI z评分校正）。每个等位基因的效应为0.34年（95%CI：0.03-0.64）。对于睾丸增大>3 mL的发作，观察到类似的趋势，但未达到显著性。UGT 2B 17的CNV是影响男性阴毛初长时间的因素。
Only a few genetic loci are known to be associated with male pubertal events. The ability of excreting testosterone (T) and other steroids in the urine depends on sulfation and glucuronidation. One of several essential glucuronidases is encoded by the UGT2B17 gene. In a preliminary report, we found that homozygous deletion of UGT2B17 in boys was associated with lower urinary excretion of T. We hypothesized that boys with a lower glucuronidation capacity may have altered androgen action and excretion affecting pubarche, as this represents a T-dependent event. 668 healthy boys (cross-sectional) aged 6.1–21.9 years (COPENHAGEN puberty study conducted from 2005 to 2006) were included. 65 of the boys where followed longitudinally every 6 months. Participants were genotyped for UGT2B17 copy number variation (CNV). Clinical pubertal staging including orchidometry, anthropometry and serum reproductive hormone levels. 59 of the 668 boys (8.8%) presented with a homozygous deletion of UGT2B17 (del/del). These boys experienced pubarche at a mean age of 12.73 years (12.00–13.46) vs 12.40 years (12.11–12.68) in boys heterozygous for deletion of UGT2B17 (del/ins) vs 12.06 years (11.79–12.33) in boys with the wild-type genotype (ins/ins) (P = 0.029, corrected for BMI z-score). The effect accounted for 0.34 years delay per allele (95% CI: 0.03–0.64). A comparable trend was observed for onset of testicular enlargement >3 mL but did not reach significance. CNV of UGT2B17 is a factor contributing to the timing of male pubarche.