A systematic literature search was performed to identify transmission disequilibrium tests on the short/long (S/L) 5-HTTLPR polymorphism in relation to autism.
Although there was a significant association between 5-HTTLPR polymorphism and autism risk under the dominant model after removing the studies causing heterogeneity, the significance did not exist after Bonferroni's correction.
The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5-HT signaling, and genetic variations in SERT are associated with various disorders including depression, anxiety, and autism.
In order to further elucidate the relationship between the 5-HTTLPR variant and autism risk, we undertook a thorough study of parent-of-origin effects, maternal genotype effects, and offspring genotype effects in a sample of affected offspring from the Autism Genetic Resource Exchange (AGRE).
The serotonin transporter promoter length polymorphism (5-hydroxytryptamine transporter length polymorphism; 5-HTTLPR) has long been implicated in autism and other psychiatric disorders.
This is the first South African study of autistic individuals of different ethnic backgrounds that shows significant differences in allele and genotype frequencies of 5-HTTLPR.
Studies point to possible links between autism and two serotonin related genes: SLC6A4 and ITGB3 with a sex-specific genetic effect and interaction between the genes.
Within autism, rare hSERT coding variants associate with rigid-compulsive traits, suggesting both phenotypic overlap with OCD and a shared relationship with disrupted 5-HT signalling.
Rare, functional, non-synonymous variants in the human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT) gene (SLC6A4) have been identified in both autism and obsessive-compulsive disorder (OCD).
However, the interesting finding of strong linkage disequilibrium (LD) between the markers and significant disease-specific distortion in the distribution of HTT-3'UTR-SNP genotypes (T1chi(2)=5.19, P=0.02; OR=2.89, 95% CI=1.13-7.41) and the specific haplotypes of the two markers (LRS=11.85, p(c)=0.02), with higher frequencies of T/T genotype and 10-T haplotype in autistic cases suggests that either these markers or nearby markers of SLC6A4 that are in LD, may pose a risk towards autism in the Eastern Indian population.
Evidence implicates the serotonin transporter gene (SLC6A4) and the 15q11-q13 genes as candidates for autism as well as restricted repetitive behavior (RRB).
In the current study we explored the hypothesis that rare variants in SLC6A4 contribute to autism susceptibility and to rigid-compulsive behaviors in autism.
We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010).
We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010).
We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010).
Analyzing four markers in SLC6A4 and four markers in ITGB3 in 117 white family triads with autism and using sex of the proband as a PC, we found significant interaction between two markers--rs1042173 in SLC6A4 and rs3809865 in ITGB3.