Mutations of the hexose-6-phosphate dehydrogenase gene rarely cause hyperandrogenemic polycystic ovary syndrome.
Mutations of the hexose-6-phosphate dehydrogenase gene rarely cause hyperandrogenemic polycystic ovary syndrome.
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DOI：
10.1016/j.steroids.2010.10.001
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发表时间：
2011-01
期刊：
影响因子：
2.7
通讯作者：
Rosenfield, Robert L.
中科院分区：
文献类型：
--
作者：
Qin, Kenan;Rosenfield, Robert L.
己糖-6-磷酸脱氢酶（H6 PD）失活突变导致可的松还原酶缺乏症，其表现为通常使用的测试无法解释的高雄激素血症，因此类似于多囊卵巢综合征（PCOS）。本研究的目的是筛查H6 PD基因突变在PCOS患者的生化高雄激素血症。对74例PCOS患者和31例健康对照者的整个H6 PD编码序列进行直接DNA测序。结果通过PCR-限制性片段长度多态性分析得到证实，以确定变体的基因型频率。在该研究中检测到多个新的错义变体。两个外显子2变异（acccaggc缺失近端的起始密码子和D151 A）和两个外显子5变异（R453 Q和P554 L）是常见的，发生率分别为23.8%，17.1%，35.2%和16.1%。外显子2和外显子5之间存在显著的连锁不平衡。病例组和对照组之间的基因型，等位基因分布，或肾上腺功能测试的变异没有显着差异。在我们的研究中，我们没有检测到任何报告的失活突变。虽然H6 PD基因是非常多态性和错义变异是常见的，编码变异很少（<1.5%）是高雄激素血症PCOS的原因。我们建议对尿17α-羟皮质激素和皮质醇排泄量不一致的地塞米松抑制性肾上腺高雄激素症患者进行遗传学研究。
Hexose-6-phosphate dehydrogenase (H6PD) inactivating mutations cause cortisone reductase deficiency, which manifests with hyperandrogenism unexplained by commonly used tests and, thus, mimics polycystic ovary syndrome (PCOS). The aim of this study was to screen for mutations of H6PD gene in PCOS patients with biochemical hyperandrogenemia. Direct DNA sequencing of the entire H6PD coding sequence was performed in 74 PCOS patients and 31 healthy controls. Results were confirmed by PCR-restriction fragment length polymorphism assay to determine the genotypic frequency of the variants. Multiple novel missense variants were detected in the study. Two exon 2 variants (acccaggc deletion proximal to the start codon and D151A) and two exon 5 variants (R453Q and P554L) were common, occurring in 23.8%, 17.1%, 35.2%, and 16.1%, respectively. There was significant linkage disequilibrium between the exon 2 and exon 5 variants. No significant differences were observed in the genotype, allele distributions, or adrenal function tests of the variants between cases and control groups. We did not detect any reported inactivating mutations in our study. Although the H6PD gene is very polymorphic and missense variants are common, coding variants rarely (<1.5%) are responsible for hyperandrogenemic PCOS. We suggest that genetic studies be reserved for patients with dexamethasone-suppressible adrenal hyperandrogenism who have a discrepancy between urinary 17α-hydroxycorticoid and cortisol excretion.
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