019) [32]. Thus, this may suggest that common SNPs in genes of choline metabolism may inf luence the demands for SMM as a methyl-group donor. Proper interpretation of the presented results on gene-gene interaction await further studies. There is a growing body of evidence that homeostasis of amino acids from Procaspase activation the arginine family may play an important role in early human development

[85]. Aberrant metabolism in environmentally sensitive pathways in individuals with CL/P who have no known metabolic disease is of growing interest [26]. A moderate association between polymorphic variants of genes for enzymes constituting an argininecitrulline cycle and risk of clefting was demonstrated in the study of Polish CL/P-affected patients [30]. The calculated OR for individuals with the gene for argininosuccinate synthetase 1 (ASS1) polymorphism rs7860909 G allele compared to AA homozygotes was 1.768 (98%CI: 1.133–2.759; p=0.01). MDR analysis provided evidence of interaction between the genes ASS1, a liver-type mitochondrial aspartate-glutamate carrier (SLC25A13), and argininosuccinate lyase (ASL) on CL/P susceptibility [30]. The overall best MDR model included two polymorphisms (the ASS1 rs 666174 and SLC25A13 rs10252573). This model had a testing balance

accuracy of 0.64 and a crossvalidation consistency of 9/10 (p=0.002). Deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier leads STA-9090 nmr to a quantitative deficiency of ASS1 without any detectable abnormalities in the ASS1 gene or ASS1 mRNA levels. We believe this is the first study Branched chain aminotransferase to evaluate DNA sequence variants in the human ASS1, ASL and SLC25A13 genes for a possible association with a structural malformation risk. These novel findings suggest a crucial role for arginine/citrullinedependent metabolic pathways in the early human development, table I. Moreover, it is important for future investigations to consider entire gene families and those in which they interact. There are several complex enzymatic mechanisms to detoxify a wide array of xenobiotics

absorbed by ingestion, inhalation, or surface contact. Maternal smoking is an established risk factor for CL/P [34,61]. S-glutathione transferases affect the detoxification of different compounds including those from cigarette smoke. Our group recently examined genes for S-glutathione transferase M1 (GSTM1) and S-glutathione transferase T1 (GSTT1), which conjugate glutathione with xenobiotics and promote their removal from the human body [21]. The frequency of the homozygous GSTM1 and GSTT1 deletions varies across populations. A significantly increased risk of giving birth to a child with CL/P was found in multiparous mothers with GSTM1(−)/GSTT1(−) and GSTM1(−)/GSTT(+) genotypes as compared to those with GSTM1(+)/GSTT1(+) genotype (OR=6.96; 95%CI:1.15–8.08, p<0.02), however, no gene-smoking interaction effects were identified.