Glutathione s-transferase polymorphisms in children with down syndrome and its influences on phenotypic diversity

Aim: We aimed to investigate the frequency of glutathione-S-transferase (GST) gene polymorphisms in children with Down syndrome, and the influences of these polymorphisms on the phenotypic diversity, and also on giving birth to a child with Down syndrome. For this purpose, we aimed to determine the relationship between disease severity and risk of occurrence of the disease by identifying the rates of polymorphism in the GSTM1, GSTT1 and GSTP1 genes in children with Down syndrome and their mothers.Methods: This study has been carried out with children clinically diagnosed and cytogenetically confirmed as Down Syndrome and with their mothers, who have been followed-up in the discipline of Pediatrics Genetics, Department of Pediatrics, Dokuz Eylul University. Healthy children and their adult mothers have been used as the control group. The study was conducted in the period between January to July, 2010. Of the children with Down Syndrome who have admitted to the hospital for routine controls, demographic characteristics, results of the cytogenetic analysis, physical examination, ophtalmologic examination, hearing test, electrocardiogram, celiac antibodies, complete blood count, thyroid function test were recorded, furthermore 2 cc EDTA blood samples were taken for testing GST polymorphisms.Results: A total of 243 subjects, as four different groups composed of 52 children with Down syndrome, 70 healthy children, 52 mothers of the children with Down Syndrome, and 69 healthy mothers, were enrolled in the study. Of the 52 patients participated in Group I (children with Down syndrome) 24 were girls and 28 were boys, aged between 1 month and 17 years (mean, 6.13 ± 4.86 years). With regard to additional pathologies, 26 (50%) of the fifty-two patients reported a cardiac disease, while 12 (23.1%) hearing loss, 20 (38.5%) ophtalmic pathologies, 4 (7.7%) gastrointestinal system pathologies, and 23 (44.2%) hypothyroidism. Homozygous deletion ( null genotype ) at the GSTM1 and GSTT1 loci were detected in 23 (44.2%) and 22 (42.3%) of the patients with Down syndrome, respectively. Ile/Val exchange was found at both two alleles of codon 105 of the GSTP1 gene in 4 (8.9%) of these patients, but only at one allele of 23 (44.2%) patients; GSTP-114 homozygous mutation was detected in none of the patients, while 10 (19.2%) patients displayed polymorphism at only one allele. Group II (healthy children) consisted of totally 70 patients, 37 (52.9%) girls and 33 (47.1%) boys, and they aged from 1 to 17 years (mean, 9.09 ± 4.98 years). GSTM1 null genotype was identified in 30 (42.9%) of the healthy children, also GSTT1 null genotype in 30 (42.9%) of the cases, while GSTP1-105 val / val genotype was detected in 5 (7.1%), and GSTP1-114 val / val polymorphism in 1 (% 1.4) of the healthy children of Group II. In comparison of the data achieved from Group I and Group II, statistically significant results could not be obtained (p = 0.88, 0.95, 0.95, 0.68, respectively). Group III (mothers of the children with Down) participants aged from 23 to 56 years (mean, 37,27± 6,77 years). Homozygous deletion was detected at GSTM1 gene in 33 (63.5%), and at GSTT1 gene in 22 (42.3%) of the subjects, while 105 val exchange was found at both alleles of GSTP1 gene in 6 (11.5%), but only at one allele in 17 (32.7%) of the subjects, also 6 (11.5%) mothers carried ala114val polymorphism at one allele. None of the mothers in this group found to have ala114val exchange at both two alleles. Group IV (mothers of the healthy children) aged between 22-50 (mean, 28,25± 6,54 years). Of these healthy mothers, 40 (58%) had GSTM1 null allele, 34 (49.3%) had GSTT1 null allele, 3 (4.3%) had polymorphism at both alleles of GSTP1-105, while 7 (10.1%) cases displayed a change at one allele of GTSP1-144. When the data achieved from analysis of Group III and Group IV mothers were compared, no statistically significant difference was evaluated (p= 0.54; 0.44; 0.32; 0.80, respectively).Conclusion: According to our study data, the frequency of GST gene polymorphisms in the patients with Down syndrome was found compatible with normal population. When compared with the healthy children participating in the study, no statistically significant difference was determined. The effects of GST gene polymorphisms on the phenotypic characteristics generally seen in the patients with Down Syndrome, could not be demonstrated. Similarly, GST gene polymorphisms detected in the mothers of children with Down and mothers of healthy children were found compatible with normal population, no significant difference was to be mentioned between the two groups. Consequently, we conclude that GST gene polymorphisms may be considered ineffective on giving birth to a child with Down syndrome.