White Perrin C
Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9063, USA.
J Clin Endocrinol Metab. 2005 Oct;90(10):5880-3. doi: 10.1210/jc.2005-0942. Epub 2005 Aug 9.
Apparent cortisone reductase deficiency (ACRD) is a rarely ascertained condition characterized by signs of androgen excess in women or children and decreased urinary excretion of cortisol metabolites compared with cortisone metabolites. These findings suggest a deficiency of 11beta-hydroxysteroid dehydrogenase type 1 (11-HSD1; encoded by the HSD11B1 gene), which normally converts cortisone to cortisol. Common polymorphisms in both HSD11B1 and the hexose-6-phosphate dehydrogenase (H6PD) gene encoding hexose-6-phosphate dehydrogenase have been found together in ACRD patients, who carry three of a possible four minor alleles at the two loci.
The objective of this study was to confirm the postulated digenic inheritance mechanism for ACRD.
This was a population-based association study (Dallas Heart Study). Subjects were genotyped for the 1971T>G polymorphism in intron 3 of HSD11B1 and the R453Q polymorphism in H6PD.
The study comprised 3551 individuals in a population-based sample (50% black, 35% white, and 15% Hispanic).
The main outcome measure was association between genotypes and risk for polycystic ovarian syndrome.
Both polymorphisms occurred more frequently than previously reported. Thus, ACRD genotypes (at least three of four minor alleles) occurred in 7.0% of subjects. There were no associations between genotype and body mass index; waist/hip ratio; visceral adiposity; measures of insulin sensitivity; levels of testosterone, FSH, or LH (in females); or risk of polycystic ovarian syndrome. There was no genotype effect on urinary free cortisol/cortisone or corticosteroid metabolite ratios, which were measured in 10 subjects, each carrying zero, three, or four minor alleles.
Previously reported associations of ACRD with HSD11B1 and H6PD alleles represent ascertainment bias. However, rare severe mutations in these genes cannot be ruled out.
表观可的松还原酶缺乏症（ACRD）是一种很少被确诊的疾病，其特征为女性或儿童出现雄激素过多的体征，且与可的松代谢产物相比，皮质醇代谢产物的尿排泄量减少。这些发现提示11β-羟类固醇脱氢酶1型（11-HSD1；由HSD11B1基因编码）缺乏，该酶通常将可的松转化为皮质醇。在ACRD患者中发现HSD11B1和编码6-磷酸己糖脱氢酶的6-磷酸己糖脱氢酶（H6PD）基因均存在常见多态性，这些患者在这两个基因座上携带了四个可能的小等位基因中的三个。
本研究的目的是证实ACRD假定的心因性遗传机制。
这是一项基于人群的关联研究（达拉斯心脏研究）。对受试者进行HSD11B1基因内含子3中1971T>G多态性和H6PD基因中R453Q多态性的基因分型。
该研究纳入了3551名基于人群的样本个体（50%为黑人，35%为白人，15%为西班牙裔）。
主要观察指标是基因型与多囊卵巢综合征风险之间的关联。
两种多态性的发生频率均高于先前报道。因此，ACRD基因型（四个小等位基因中至少三个）出现在7.0%的受试者中。基因型与体重指数、腰臀比、内脏脂肪、胰岛素敏感性指标、睾酮、促卵泡激素或促黄体生成素水平（女性）或多囊卵巢综合征风险之间均无关联。在10名分别携带零个、三个或四个小等位基因的受试者中测量的尿游离皮质醇/可的松或皮质类固醇代谢产物比值没有基因型效应。
先前报道的ACRD与HSD11B1和H6PD等位基因的关联代表了确诊偏倚。然而，不能排除这些基因中存在罕见的严重突变。
