title: [Genetic polymorphisms of GSTM1 and GSTT1 in mothers of children with isolated cleft lip with or without cleft palate].
abstract: 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.
authors.affiliation: Kilinika Pediatrii, Instytut Matki i Dziecka, Warszawa. khozyasz@alpha.net.pl
authors.forename: Kamil K
authors.initials: KK
authors.lastname: Hozyasz
authors.forename: Adrianna
authors.initials: A
authors.lastname: Mostowska
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Surowiec
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D009035:Mothers; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D005982:Glutathione Transferase; C413545:glutathione S-transferase T1