Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.
Reprod Biomed Online. 2012 Nov;25(5):527-35. doi: 10.1016/j.rbmo.2012.07.006. Epub 2012 Jul 20.
The adipokines produced from adipose tissues influence energy homeostasis, resulting in alterations of the adipokine concentrations. This process may be associated with fertility impairment, resulting in recurrent miscarriage. The present study investigated whether there was any association between the UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms, namely leptin 2549 (C/A), adeponectin 276 (G/T) and 45 (T/G) and resistin 420 (C/G) in 200 non-obese recurrent miscarriage patients and 300 ethnically matched negative controls. These markers were studied using gene-specific PCR single specific primer and restriction fragment length polymorphism. For leptin 2549 and adeponectin 276, the A allele and G allele showed 3.42-fold (P=0.0001) and 1.36-fold (P=0.036) increased risk of recurrent miscarriage, respectively. Combined analysis of UCP2 45-bp indel and leptin 2549 showed U0-L0 and U1-L0 variants to be at 2- and 3-fold increased associative risk, respectively. Combined analysis of leptin 2549 and adeponectin 276 showed L0-D0 and L0-D1 variants to be at 2- and 4-fold increased associative risk, respectively. The combination U1-L0-D1-A1-R1 was 4.39-fold higher (P=0.0007) among recurrent miscarriage patients. In conclusion, the results highlight the role of the studied adipokine and UCP2 polymorphisms in recurrent miscarriage among the North Indian non-obese population. Pregnancy invokes a large shift in maternal metabolism. The normal concentrations of adipokines, which maintain the integrity of the hypothalamus-pituitary-gonadal axis, regular ovulatory processes and successful embryo implantation, are altered because of the influence of energy homeostasis, which in turn leads to fertility impairment and recurrent miscarriage of unknown aetiology. Recurrent miscarriage is reported in higher frequency among obese women. The UCP2 45-bp indel polymorphism and the adipokine gene polymorphisms namely leptin 2549 (C/A), adeponectin 276 (G/T), adeponectin 45 (T/G) and resistin 420 (C/G) have been shown to be associated with obesity. Most of the adipokine-related studies done previously have taken into consideration the metabolic function and obesity. However, there exist very few studies to evaluate the role of adipokines in non-obese recurrent miscarriage with no cause of repeated pregnancy losses. The present study focused at evaluating the independent effect of these single-nucleotide polymorphisms in non-obese women undergoing recurrent miscarriage.
脂肪组织产生的脂肪因子会影响能量平衡，导致脂肪因子浓度发生变化。这一过程可能与生育能力受损有关，导致反复流产。本研究旨在探讨 UCP2 45-bp 插入缺失多态性与脂肪因子基因多态性（瘦素 2549（C/A）、脂联素 276（G/T）和 45（T/G）以及抵抗素 420（C/G））之间是否存在关联，在 200 名非肥胖复发性流产患者和 300 名种族匹配的阴性对照组中进行了研究。这些标记物使用基因特异性 PCR 单特异性引物和限制性片段长度多态性进行了研究。对于瘦素 2549 和脂联素 276，A 等位基因和 G 等位基因分别显示出 3.42 倍（P=0.0001）和 1.36 倍（P=0.036）的复发性流产风险增加。UCP2 45-bp 插入缺失与瘦素 2549 的联合分析表明，U0-L0 和 U1-L0 变体的关联风险分别增加了 2 倍和 3 倍。瘦素 2549 和脂联素 276 的联合分析表明，L0-D0 和 L0-D1 变体的关联风险分别增加了 2 倍和 4 倍。复发性流产患者中 U1-L0-D1-A1-R1 组合的发生率增加了 4.39 倍（P=0.0007）。综上所述，研究结果强调了所研究的脂肪因子和 UCP2 多态性在印度北部非肥胖人群中复发性流产中的作用。妊娠会引起母体代谢的巨大变化。正常的脂肪因子浓度可以维持下丘脑-垂体-性腺轴的完整性、规律的排卵过程和胚胎着床的成功，但由于能量平衡的影响，这些脂肪因子的浓度发生了改变，从而导致生育能力受损和原因不明的复发性流产。肥胖女性中报告的复发性流产频率更高。UCP2 45-bp 插入缺失多态性和脂肪因子基因多态性，即瘦素 2549（C/A）、脂联素 276（G/T）、脂联素 45（T/G）和抵抗素 420（C/G），与肥胖有关。以前进行的大多数与脂肪因子相关的研究都考虑了代谢功能和肥胖。然而，很少有研究评估非肥胖复发性流产中脂肪因子在无反复妊娠丢失原因中的作用。本研究集中评估了这些单核苷酸多态性在非肥胖复发性流产女性中的独立作用。
