A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11β-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome
A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11β-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome
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DOI：
10.1210/jc.2004-1523
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发表时间：
2005-07-01
影响因子：
5.8
通讯作者：
Escobar-Morreale, HF
中科院分区：
文献类型：
--
作者：
San Millán, JL;Botella-Carretero, JI;Escobar-Morreale, HF
背景：己糖-6-磷酸脱氢酶基因(H6PD)的R453Q变异和11β-羟基类固醇脱氢酶(11βHSD)1型基因(HSD11B1)的83557insA突变相互作用，导致皮质醇还原酶缺乏症(CRD)。CRD是一种罕见的疾病，其特征是多囊卵巢综合征(PCOS)样的表型。目的：研究PCOS的这些突变。设计：病例对照研究。背景：该研究在一家学术医院进行。参与者：共有116名PCOS患者和76名非高雄激素对照参与。主要观察指标：基因分布以及基因类型对临床和生化变量的影响，以及对临床和生化变量的影响结果：4名对照组和5名患者在H6PD R453Q和HSD11B1 83557insA的4个突变等位基因中发现了3个突变等位基因，HSD11B1 83557insA是一些CRD患者中观察到的基因。对这9名女性中的6名进行了11βHSD氧化还原酶活性的估计，排除了CRD。此外，H6PD R453Q和HSD11B183557insA两种基因单独或组合对11βHSD氧化还原酶活性均无影响。H6PD R453Q基因型(R/R、R/Q和Q/Q)在对照组和对照组中的分布有差异(42%的对照组和63%的多囊卵巢综合征患者为R/R；53%的对照组和31%的多囊卵巢综合征患者为R/Q；5%的对照组和6%的多囊卵巢综合征患者为Q/Q；X(2)=9.1P=0.011)。与携带Q453等位基因的患者相比，携带R453等位基因的患者皮质醇和17-羟孕酮水平升高，但在对照组中没有观察到这些差异。结论：H6PD R453Q变异和HSD11B1 83557insA突变的双重三等位基因并不一定导致CRD。相反，H6PD R453Q变异与PCOS相关，并可能通过影响肾上腺活动而影响其表型。
Context: The R453Q variant in the hexose-6-phosphate dehydrogenase gene (H6PD) and 83557insA mutations in 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) type 1 gene (HSD11B1) interact, resulting in cortisone reductase deficiency (CRD), a rare disorder characterized by a polycystic ovary syndrome (PCOS)-like phenotype.Objective: The objective was to study these mutations in PCOS.Design: The design was a case-control study.Setting: The study was conducted in an academic hospital.Participants: A total of 116 PCOS patients and 76 nonhyperandrogenic controls participated.Main Outcome Measures: Genotype distributions and influence of genotypes on clinical and biochemical variables and, in 28 patients and 12 controls, estimates of 11 beta HSD oxoreductase activity were the main outcome measures.Results: Four controls and five patients presented three of four mutant alleles in H6PD R453Q and HSD11B1 83557insA, which is the genotype observed in some subjects with CRD. Estimates of 11 beta HSD oxoreductase activity were measured in six of these nine women, ruling out CRD. Moreover, H6PD R453Q and HSD11B1 83557insA genotypes, either separately or in combination, did not influence 11 beta HSD oxoreductase activity. The distribution of H6PD R453Q genotypes (R/R, R/Q, and Q/Q) was different in patients and controls (42% of controls and 63% of PCOS patients were R/R; 53% of controls and 31% of PCOS patients were R/Q; and 5% of controls and 6% of PCOS patients were Q/Q; chi(2) = 9.1; P = 0.011). Patients homozygous for R453 alleles presented with increased cortisol and 17-hydroxyprogesterone levels, compared with carriers of Q453 alleles, but these differences were not observed in controls. On the contrary, HSD11B1 83557insA genotypes were not associated with PCOS and did not influence any phenotypic variable.Conclusions: Digenic triallelic genotypes of the H6PD R453Q variant and HSD11B1 83557insA mutation do not always cause CRD. On the contrary, the H6PD R453Q variant is associated with PCOS and might influence its phenotype by influencing adrenal activity.