Hozyasz Kamil K, Mostowska Adrianna, Surowiec Zbigniew, Jagodziński Paweł P
Kilinika Pediatrii, Instytut Matki i Dziecka, Warszawa.
Przegl Lek. 2005;62(10):1019-22.
Orofacial clefts are one of the most common developmental malformations (OMIM #119530, #119540), which aetiology is very complex and associated with both genetic and environmental factors. One of the main environmental factors increasing the risk of having a child with an oral cleft is maternal cigarette smoking. The effect of maternal smoking may be modified by genes involved in biotransformation of toxic compounds derived from tobacco. Very important role in this process is played by S-glutathione transferase M1 (GSTM1) and S-glutathione transferase T1 (GSTT1) which conjugate glutathione with xenobiotics and promote their removal from human body. The aim of this study was frequency analysis of homozygous deletion of GSTM1 and GSTT1 genes in women having infants with ororfacial clefts and in control group. In this case-control study we used DNA isolated from peripheral blood lymphocytes of 121 mothers having children with isolated cleft lip with or without cleft palate and from 80 control mothers. The common deletions of GSTM1 and GSTT1 were determined by polymerase chain reaction and agarose gel separation. The prevalence of genotype GSTM1(-)/GSTT1(-) was higher in mothers of children with cleft (6.6%) compared to controls (3.7%, p>0.05). Among multiparous mothers of children with cleft (one child with birth defect and at least 2 healthy children, mean number of children - 4) the prevalence of genotype GSTM1(+)/GSTTI(+) was significantly reduced (31.0% vs. 58.7%, p=0.011). A significantly increased risk of giving birth to a child with cleft was found in multiparous subgroup of mothers with GSTM1(-)/GSTT1(-) and GSTM1(-)/ GSTT1(+) genotypes as compared to those with GSTM1(+)IGSTT1(+) genotype (OR 6.96; 95%CI: 1.33-36.57, p<0.01 i 3.05; 95%CI: 1.153-8.05, p<0.02 respectively). We did not observe a significant correlation between smoking status, GSTM1/GSTT1 genotypes and risk of orofacial clefts. Our results suggest that homozygous deletions of GSTM1 and GSTT1 in mother genome might increase the risk of having child with cleft lip with or without cleft palate.
口腔颌面裂是最常见的发育畸形之一（在线人类孟德尔遗传数据库编号#119530、#119540），其病因非常复杂，与遗传和环境因素均有关联。增加生育患口腔颌面裂患儿风险的主要环境因素之一是母亲吸烟。母亲吸烟的影响可能会受到参与烟草衍生有毒化合物生物转化的基因的调节。S-谷胱甘肽转移酶M1（GSTM1）和S-谷胱甘肽转移酶T1（GSTT1）在这一过程中发挥着非常重要的作用，它们使谷胱甘肽与外来化合物结合，并促进其从人体排出。本研究的目的是对患有口腔颌面裂婴儿的女性和对照组中GSTM1和GSTT1基因纯合缺失的频率进行分析。在这项病例对照研究中，我们使用了从121名生育单纯唇裂伴或不伴腭裂患儿的母亲外周血淋巴细胞中分离的DNA，以及80名对照母亲的DNA。通过聚合酶链反应和琼脂糖凝胶分离来确定GSTM1和GSTT1的常见缺失情况。与对照组（3.7%，p>0.05）相比，患口腔颌面裂患儿母亲中基因型GSTM1(-)/GSTT1(-)的患病率更高（6.6%）。在生育患口腔颌面裂患儿的经产妇母亲（一个孩子有出生缺陷且至少有2个健康孩子，平均孩子数-4）中，基因型GSTM1(+)/GSTTI(+)的患病率显著降低（31.0%对58.7%，p=0.011）。与基因型为GSTM1(+)/GSTT1(+)的母亲相比，基因型为GSTM1(-)/GSTT1(-)和GSTM1(-)/GSTT1(+)的经产妇亚组生育患口腔颌面裂患儿的风险显著增加（OR分别为6.96；95%置信区间：1.33-36.57，p<0.01和3.05；95%置信区间：1.153-8.05，p<0.02）。我们未观察到吸烟状况、GSTM1/GSTT1基因型与口腔颌面裂风险之间存在显著相关性。我们的研究结果表明，母亲基因组中GSTM1和GSTT1的纯合缺失可能会增加生育单纯唇裂伴或不伴腭裂患儿的风险。
