Abstract：
BACKGROUND: Premature Ovarian Insufficiency (POI) is associated with infertility. Little is known about the potential circulating biomarkers that could be used to predict POI. We have investigated the possible association between white and red blood cells, platelet indices, and eight established single nucleotide polymorphisms (SNPs) associated with POI risk.
METHODS: 117 women with premature menopause (PM) and 183 healthy women without a history of menopause before age 40 were recruited for this study. The tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS PCR) and allele-specific oligonucleotides-polymerase chain reaction (ASO-PCR) were carried out for genotyping for eight SNPs reported to be associated with POI. Decision tree analysis was applied to test the diagnostic value of hematological parameters to identify the risk of POI.
RESULTS: Women with POI had lower neutrophil (NEUT) and white blood cell (WBC), whereas red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) were higher. Platelet (PLT) count was also lower in affected women. Our data also indicated that HGB and HCT count were significantly associated with rs16991615 and rs244715. Mean Platelet volume (MPV) and platelet distribution width (PDW) were associated with rs244715, rs1046089, rs4806660, and rs2303369. The rs16991615 was also associated with RBC count, and rs451417 was associated with NEUTs. The decision tree (DT) model reveals that women with the NEUT count at a cut-off value of less than 2.8 and HCT equal to or more than 38.7% could be identified as high-risk cases for POI. Overall, we found the DT approach had a sensitivity = 85%, specificity = 72%, and accuracy = 74%.
CONCLUSIONS: The genetic variants involved in POI are associated with changes in reproductive hormone levels and with changes in hematological indices.
METHODS: 117 women with premature menopause (PM) and 183 healthy women without a history of menopause before age 40 were recruited for this study. The tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS PCR) and allele-specific oligonucleotides-polymerase chain reaction (ASO-PCR) were carried out for genotyping for eight SNPs reported to be associated with POI. Decision tree analysis was applied to test the diagnostic value of hematological parameters to identify the risk of POI.
RESULTS: Women with POI had lower neutrophil (NEUT) and white blood cell (WBC), whereas red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) were higher. Platelet (PLT) count was also lower in affected women. Our data also indicated that HGB and HCT count were significantly associated with rs16991615 and rs244715. Mean Platelet volume (MPV) and platelet distribution width (PDW) were associated with rs244715, rs1046089, rs4806660, and rs2303369. The rs16991615 was also associated with RBC count, and rs451417 was associated with NEUTs. The decision tree (DT) model reveals that women with the NEUT count at a cut-off value of less than 2.8 and HCT equal to or more than 38.7% could be identified as high-risk cases for POI. Overall, we found the DT approach had a sensitivity = 85%, specificity = 72%, and accuracy = 74%.
CONCLUSIONS: The genetic variants involved in POI are associated with changes in reproductive hormone levels and with changes in hematological indices.
摘要：
背景：过早卵巢功能不全（POI）与不孕症有关。关于可用于预测POI的潜在循环生物标志物知之甚少。我们已经调查了白细胞和红细胞之间可能的关联，血小板指数,和八个已确定的单核苷酸多态性（SNP）与POI风险相关。
方法：本研究招募了117名在40岁之前有过早绝经（PM）的女性和183名没有绝经史的健康女性。进行了四引物扩增难治性突变系统-聚合酶链反应（TetraARMSPCR）和等位基因特异性寡核苷酸-聚合酶链反应（ASO-PCR），以对据报道与POI相关的八个SNP进行基因分型。应用决策树分析检验血液学参数的诊断价值,以识别POI的风险。
结果：患有POI的女性中性粒细胞（NEUT）和白细胞（WBC）较低，而红细胞（RBC），血红蛋白（HGB），血细胞比容(HCT),平均红细胞体积（MCV），平均细胞血红蛋白（MCH）较高。受影响妇女的血小板（PLT）计数也较低。我们的数据还表明HGB和HCT计数与rs16991615和rs244715显著相关。平均血小板体积(MPV)和血小板分布宽度(PDW)与rs244715、rs1046089、rs4806660和rs2303369相关。rs16991615也与红细胞计数有关，rs451417与NEUTs相关。决策树（DT）模型显示，NEUT计数的截止值小于2.8且HCT等于或大于38.7％的女性可以被确定为POI的高风险病例。总的来说,我们发现DT方法的灵敏度=85%，特异性=72%，准确度=74%。
结论：参与POI的遗传变异与生殖激素水平的变化和血液学指标的变化有关。
方法：本研究招募了117名在40岁之前有过早绝经（PM）的女性和183名没有绝经史的健康女性。进行了四引物扩增难治性突变系统-聚合酶链反应（TetraARMSPCR）和等位基因特异性寡核苷酸-聚合酶链反应（ASO-PCR），以对据报道与POI相关的八个SNP进行基因分型。应用决策树分析检验血液学参数的诊断价值,以识别POI的风险。
结果：患有POI的女性中性粒细胞（NEUT）和白细胞（WBC）较低，而红细胞（RBC），血红蛋白（HGB），血细胞比容(HCT),平均红细胞体积（MCV），平均细胞血红蛋白（MCH）较高。受影响妇女的血小板（PLT）计数也较低。我们的数据还表明HGB和HCT计数与rs16991615和rs244715显著相关。平均血小板体积(MPV)和血小板分布宽度(PDW)与rs244715、rs1046089、rs4806660和rs2303369相关。rs16991615也与红细胞计数有关，rs451417与NEUTs相关。决策树（DT）模型显示，NEUT计数的截止值小于2.8且HCT等于或大于38.7％的女性可以被确定为POI的高风险病例。总的来说,我们发现DT方法的灵敏度=85%，特异性=72%，准确度=74%。
结论：参与POI的遗传变异与生殖激素水平的变化和血液学指标的变化有关。
