Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome
Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome
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DOI：
10.1111/j.1365-2265.2006.02547.x
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发表时间：
2006-07-01
影响因子：
3.2
通讯作者：
McCarthy, Mark I.
中科院分区：
文献类型：
--
作者：
Draper, Nicole;Powell, Brenda L.;McCarthy, Mark I.
目的可的松还原酶缺乏症（CRD）是一种罕见的皮质醇代谢异常，与多囊卵巢综合征（PCOS）有着密切的表型相似性。由于有证据表明CRD是由涉及编码11 β-羟基类固醇脱氢酶1型（HSD 11B 1）和己糖-6-磷酸脱氢酶（H6 PD）的基因的双基因突变引起的，我们试图确定这些基因中的CRD相关变体是否单独或组合影响PCOS的易感性。以家庭为基础的协会和量化-一个英国病例样本包括256个从PCOS后代确定的核心家庭和213个单胎PCOS病例加上549个对照受试者。在HSD 11B 1（rs 12086634）和H6 PD（rs6688832）中的CRD相关变体。Tehran测定与内部放射免疫分析使用乙醚提取和葡聚糖涂层carbon separation.Results病例对照分析显示，PCOS和对照组之间的基因型分布无差异rs 12086634或rs6688832（均P = 0.84）。3%的病例和2.4%的对照有被认为是CRD特征的基因型组合（两个位点有三个或更多变异等位基因）（P = 0.73）。有没有偏离预期的家庭为基础的关联研究，并没有显着的关联基因型（单独或组合）和BMI，WHR或testosterone.Conclusions的HSD 11B 1和H6 PD型的变异，虽然牵连的CRD的原因，不影响PCOS的易感性。这些基因中的其他变异似乎是CRD发展所必需的。
Objective There are close phenotypic similarities between cortisone reductase deficiency (CRD), a rare abnormality of cortisone metabolism, and polycystic ovary syndrome (PCOS). As there is evidence that CRD results from digenic mutations involving the genes encoding 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) and hexose-6-phosphate dehydrogenase (H6PD), we sought to establish whether CRD-associated variants in these genes, individually or in combination, influence susceptibility to PCOS.Design Case-control, family-based association and quantitative-trait analyses.Patients A UK case sample comprising 256 nuclear families ascertained from a PCOS offspring and 213 singleton PCOS cases plus 549 control subjects.Measurements All subjects were genotyped for CRD-related variants in HSD11B1 (rs12086634) and H6PD (rs6688832). Testosterone was measured with an in-house radioimmunoassay using ether extraction and dextran-coated charcoal separation.Results Case-control analyses revealed no differences in genotype distribution between PCOS and controls for rs12086634 or rs6688832 (both P = 0.84). Three per cent of cases and 2.4% of controls had genotype combinations (three or more variant alleles at the two sites) considered characteristic of CRD (P = 0.73). There were no departures from expectation in the family-based association studies, and no significant associations between genotypes (individually or in combination) and BMI, WHR or testosterone.Conclusions The variants in HSD11B1 and H6PD typed, though implicated in causation of CRD, do not influence susceptibility to PCOS. It seems likely that additional variants within these genes are required for the development of CRD.