The association of polymorphism of catechol-O-methyltransferase and karyotype abnormalities in disabled children

Introduction Intellectual disability (ID) remains one of the most lifelong handicaps. The incidence of ID is estimated currently to be around 1–3% of the population; 5–30% of moderate to severe ID can be accounted for by chromosomal disorders and the majority are associated with malformations, growth retardation, dysmorphism, and possibly family history of similar occurrence. Catechol-O-methyltransferase (COMT) plays an important role in breakdown of dopamine in the prefrontal cortex. COMT is an intracellular enzyme located in the postsynaptic neuron; any compound with a catechol structure, such as catechol estrogens and catechol-containing flavonoids, are substrates of COMT. This gene is involved in at least three metabolic pathways to include the following: tyrosine metabolism, estrogen metabolism, and dopamine metabolism. In the brain, COMT-dependent dopamine degradation is of particular importance in brain regions with low expression of the presynaptic dopamine transporter, such as the prefrontal cortex; this process is believed to take place in postsynaptic neurons as COMT is located intracellularly. Patients and methods The current study was carried out on 40 mentally retarded patients with/without stigmata of dysmorphology and malformations to detect chromosomal abnormalities and to clarify the association between the COMT gene polymorphism and intelligence quotient level. Results ID with congenital anomalies was present in 70% of the patients studied, whereas major anomalies and minor anomalies were detected in 2.5 and 67.5%, respectively. The results of karyotyping by conventional Giemsa trypsin staining banding showed that 87.5% of the patients studied had a normal karyotype and 12.5% had chromosomal abnormalities. The frequency of the wild COMT (HH) genotype (55%) was the highest, followed by the heterozygous mutant (HL) genotype (37.5%) and the homozygous mutant (LL) genotype (7.5%). The results of COMT genotyping by PCR-RFLP showed a significantly higher mean intelligence quotient score in patients with the wild (HH) genotype (42.1±8.9) compared with those with mutant (HL, LL) genotypes (36.2±11.8) (P=0.14). Conclusion The results of this study need to be confirmed by subsequent studies investigating a larger number of patients in each group to avoid statistical interference and bias. More trials are needed to clearly delineate the magnitude of the role of COMT gene polymorphism in the pathogenesis of ID that might lead to development of realistic therapies or preventive strategies.