Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India.
Reprod Biomed Online. 2013 Apr;26(4):313-22. doi: 10.1016/j.rbmo.2012.12.004. Epub 2012 Dec 22.
Glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase Mu 1 (GSTM1) enzymes of the glutathione detoxification pathway protect the embryo from oxidative stress. This study investigated GSTT1 and GSTM1 in relation to their role in conferring genetic susceptibility to pregnancy loss. In a case-control study, 174 early pregnancy loss (EPL) patients, of which 130 were recurrent pregnancy loss (RPL) patients, and 180 healthy controls were investigated. Null genotypes of GSTT1 and GSTM1 were identified in duplex PCR reaction systems. Age-adjusted odds ratios (aOR) were calculated by logistic regression analysis. A meta-analysis was also conducted. The GSTT1 null genotype was significantly associated with EPL (aOR 4.47, P=0.004) and RPL (aOR 4.39, P=0.006). No significant association of the GSTM1 null genotype was found with RPL. In a meta-analysis study, the presence of the GSTM1 null genotype was shown to be a risk for RPL. The GSTT1 null genotype was not found to be a risk factor for pregnancy loss in the pooled population but its association with RPL was found in the Indian population. This study suggests that women carriers of GSTT1 and GSTM1 null genotypes are more often at genetic risk of pregnancy loss. Glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1), enzymes of detoxification pathway, protect the embryo from oxidative stress. In the present study we have investigated GSTT1 and GSTM1 in relation to their role in conferring genetic susceptibility for early pregnancy loss (EPL) and recurrent pregnancy loss (RPL). Meta-analysis on the polymorphisms was conducted to support our findings that the presence of mutant genotypes at this site increases the risk of pregnancy loss. The GSTT1 null genotype was significantly associated with both EPL and RPL. In the meta-analysis, the overall result showed that the association between GSTM1 null genotype and risk for RPL was statistically significant. On comparing the GSTT1 studies, great heterogeneity was found between studies. A subgroup analysis was performed based on ethnicity. Our results showed a significantly increased risk with the GSTT1 null genotype in the Indian population, but no risk was found in the pooled population. In conclusion, the data of the present study clearly suggest that GSTT1 and GSTM1 polymorphisms are genetic risk factors for pregnancy loss in the study population.
谷胱甘肽 S-转移酶 theta 1（GSTT1）和谷胱甘肽 S-转移酶 Mu 1（GSTM1）是谷胱甘肽解毒途径的酶，可保护胚胎免受氧化应激。本研究探讨了 GSTT1 和 GSTM1 在赋予妊娠丢失遗传易感性方面的作用。在病例对照研究中，对 174 例早期妊娠丢失（EPL）患者（其中 130 例为复发性妊娠丢失（RPL）患者）和 180 例健康对照进行了研究。在双 PCR 反应系统中确定 GSTT1 和 GSTM1 的无效基因型。通过逻辑回归分析计算年龄调整后的优势比（aOR）。还进行了荟萃分析。GSTT1 无效基因型与 EPL（aOR 4.47，P=0.004）和 RPL（aOR 4.39，P=0.006）显著相关。GSTM1 无效基因型与 RPL 无显著相关性。荟萃分析研究表明，GSTM1 无效基因型的存在是 RPL 的危险因素。在汇总人群中，GSTT1 无效基因型未被发现是妊娠丢失的危险因素，但在印度人群中发现其与 RPL 相关。本研究表明，携带 GSTT1 和 GSTM1 无效基因型的女性更易受到妊娠丢失的遗传风险。谷胱甘肽 S-转移酶 theta 1（GSTT1）和谷胱甘肽 S-转移酶 mu 1（GSTM1）是解毒途径的酶，可保护胚胎免受氧化应激。在本研究中，我们研究了 GSTT1 和 GSTM1 在赋予早期妊娠丢失（EPL）和复发性妊娠丢失（RPL）遗传易感性方面的作用。对该位点的多态性进行了荟萃分析，以支持我们的发现，即该位点的突变基因型的存在增加了妊娠丢失的风险。GSTT1 无效基因型与 EPL 和 RPL 均显著相关。荟萃分析的总体结果表明，GSTM1 无效基因型与 RPL 风险之间存在统计学显著关联。在比较 GSTT1 研究时，研究之间存在很大的异质性。根据种族进行了亚组分析。我们的结果表明，在印度人群中，GSTT1 无效基因型的风险显著增加，但在汇总人群中未发现风险。总之，本研究的数据清楚地表明，GSTT1 和 GSTM1 多态性是研究人群中妊娠丢失的遗传危险因素。
