ABSTRACT
Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with several neurodevelopmental disorders and their role in neuronal development is being investigated. To assess the possible influence of cytokines on the onset of intellectual disability (ID), we studied the polymorphisms of thirteen proinflammatory cytokine genes in 81 patients and 61 healthy controls. We demonstrated a significant association of interleukin-6 (IL-6) single-nucleotide polymorphism (SNP) (-174 G/C and nt565 G/A), and interleukin-1 receptor antagonist (IL-1RA) (Mspa-I 11100) SNP with ID. Moreover, the IL-6 SNPs is an unfavorable genetic predisposition for females. The evaluation of circulating levels of IL-6 and IL-1RA showed that the serum concentrations of IL-6 were significantly higher in ID patients than in controls. These data suggest that functional cytokine gene polymorphisms may influence the development of ID.
Subject(s)
Cytokines/genetics , Genetic Predisposition to Disease , Intellectual Disability/genetics , Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-6/genetics , Adolescent , Alleles , Case-Control Studies , Child , Cytokines/blood , Cytokines/metabolism , Female , Genotype , Haplotypes , Humans , Intellectual Disability/diagnosis , Intellectual Disability/metabolism , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin 1 Receptor Antagonist Protein/metabolism , Male , Polymorphism, Single NucleotideABSTRACT
Symptoms of attention-deficit hyperactivity disorder (ADHD) have been found in several studies of children with intellectual disabilities (ID) but the two diseases are not always associated. Several lines of evidence implicate the involvement of brain-derived neurotrophic factor (BDNF) in ADHD, and it may also be relevant in ID due to its known involvement in the development of the central nervous system (CNS) and in learning/memory functions. We genotyped paediatric patients with ADHD and ID for the Val66Met and 270 C/T polymorphisms in BDNF. Diagnosis of ADHD and ID was confirmed by the clinicians in accordance with DSM-IV criteria. The G/A genotype of the Val66Met SNP was associated with both ADHD and ID, and the G allele was significantly associated with ADHD. The C/C genotype of the C270T SNP was significantly overrepresented in both ADHD and ID groups compared with the controls. Data suggest that both BDNF polymorphisms could play a role in the etiology of ADHD. In addition, we present the first results suggesting that these BDNF SNPs are significantly associated with ID.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Brain-Derived Neurotrophic Factor/genetics , Intellectual Disability/genetics , Adolescent , Adult , Alleles , Attention Deficit Disorder with Hyperactivity/epidemiology , Child , Child, Preschool , DNA/genetics , Female , Gene Frequency , Genotype , Humans , Intellectual Disability/epidemiology , Italy/epidemiology , Male , Neuropsychological Tests , Polymorphism, Genetic/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sex Factors , Wechsler Scales , Young AdultABSTRACT
This study examines the possible relationship existing between the HLA-DR gene and attention deficit hyperactivity disorder (ADHD) and/or mental retardation (MR). The diagnosis of ADHD and mental retardation were established through clinical interviews with the parents, children and teachers, according to the criteria in DSM-IV. HLA-DRB1 genotyping was performed both by polymerase chain reaction-sequence specific primers (PCR-SSP) and by sequence based typing (SBT) in a cohort of 81 affected children and a sample of 100 healthy controls. Here, we report a positive association of HLA-DR4 with ADHD but not with MR. The study adds confirmation to the role of the HLA-DRB1 in the etiology of some types of childhood neuropsychiatric illnesses.
