Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity
Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity
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DOI：
10.1210/jc.2003-031252
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发表时间：
2004-06-01
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;Cortón, M;Escobar-Morreale, HF
我们评估了多囊卵巢综合征（PCOS）与15个基因组变异之间的可能关联，这些变异先前被描述为影响胰岛素抵抗、肥胖和/或2型糖尿病。对72例PCOS患者和42例健康对照进行了15个基因的基因分型，这些基因分别编码对氧氧化酶（3个变异）、浆细胞分化抗原糖蛋白、人山梨素和含SH3结构域1、纤溶酶原激活物抑制剂-1、过氧化物酶体增殖物激活受体- γ - 2、蛋白酪氨酸磷酸酶1B（2个变异）、脂联素（2个变异）、IGF1、IGF2、IGF1受体和IGF2受体。与对照组相比，PCOS患者对氧磷酶- 108T变异纯合子频率更高（36.6%比9.5%,P = 0.002）， IGF2中ApaI变异G等位基因纯合子频率更高（62.9%比38.1%,P = 0.018）。对氧磷酶是一种血清抗氧化酶，由于- 108T等位基因导致对氧磷酶表达降低，这种氧化应激的增加可能导致胰岛素抵抗。IGF2中ApaI变异的G等位基因可能增加IGF2的表达，IGF2刺激肾上腺和卵巢雄激素分泌。总之，paraoxonase - 108c - >t变异和IGF2基因ApaI多态性与PCOS相关，并可能导致这种常见疾病中氧化应激、胰岛素抵抗和高雄激素症的增加。
We have evaluated the possible association of polycystic ovary syndrome ( PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus.Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase ( three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B ( two variants), adiponectin ( two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor.Compared with controls, PCOS patients were more frequently homozygous for the - 108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because - 108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion.In conclusion, the paraoxonase - 108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.