Diabetes, Obesity and Human Reproduction Research Group, Universidad de Alcalá & Hospital Universitario Ramon y Cajal & Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, 28034 Madrid, Spain.
Gene. 2012 Apr 10;497(1):38-44. doi: 10.1016/j.gene.2012.01.047. Epub 2012 Jan 28.
Hexose-6-phosphate dehydrogenase (H6PDH) influences 11β-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (χ(2)=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (χ(2)=3.95, P=0.047), especially within the PCOS subgroup (χ(2)=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R(2)=0.490; χ(2)=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10-1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27-0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism.
己糖-6-磷酸脱氢酶（H6PDH）影响 11β-羟类固醇脱氢酶活性，这是皮质醇外周代谢中的关键酶，可调节脂肪组织中的胰岛素敏感性。为了研究 H6PDH 基因（H6PD）中 R453Q 和 D151A 多态性与多囊卵巢综合征（PCOS）的关联及其对临床和代谢变量的影响，我们对 237 例 PCOS 患者和 135 例对照女性进行了 H6PD 的 R453Q（rs6688832）和 D151A（rs34603401）多态性的基因分型。R453Q 基因型在患者和对照组中的分布不同（χ²=9.55，P=0.002）。D151A 基因型在 PCOS 患者和对照组中的分布均匀，但在非肥胖和肥胖女性中的分布不同（χ²=3.95，P=0.047），尤其是在 PCOS 亚组中（χ²=4.65，P=0.031）。向后逐步似然比逻辑回归模型（Nagelkerke 的 R²=0.490；χ²=164；P<0.0001）保留了游离睾酮（OR=1.13；95%CI：1.10-1.17）和 H6PD Q453 等位基因（OR=0.46；95%CI：0.27-0.79）作为 PCOS 的统计学显著预测因子，而胰岛素抵抗的稳态模型评估和 H6PD D151A 变体被模型排除。两种 H6PD 变体均与多种表型变量相关，包括空腹胰岛素、胰岛素抵抗的稳态模型评估和雄烯二酮水平。总之，H6PD 基因的 R453Q 和 D151A 变体分别与 PCOS 和肥胖相关，并且可能通过影响肥胖、胰岛素抵抗和高雄激素血症来导致 PCOS 表型。
