Abstract
Surface proteins containing leucine-rich repeat (LRR) are essential for the formation of synapses. Therefore, proteins containing aberrant LRR regions are speculated to cause synaptic dysfunction, an abnormality often associated with Autism spectrum disorder (ASD). LRR transmembrane 3 (LRRTM3) genetic variants showed association with ASD in the Caucasoid probands. We for the first time, analyzed two LRRTM3 genetic variants, rs1925575, and rs1925608, in Indian subjects (N=1048), including ASD probands (N=270), their parents (N=428), and healthy controls (N=350). ASD severity was assessed by the Childhood Autism Rating Scale2-standard test (CARS2-ST). Peripheral blood was collected after obtaining informed written consent for participation, and target sites were amplified by polymerase chain reaction using genomic DNA. Amplicons generated were subjected to differential digestion using a restriction enzyme, and the genotype data were analyzed for association with ASD by both population and family-based methods. Frequencies of rs1925608 and rs1925575 "CC" genotypes and C-C haplotype were higher in the probands (P=0.001). Analysis of parental data revealed a higher frequency of rs1925575 "T" in the fathers (P=0.01) and biased paternal transmission of rs1925575 "C" allele (P=0.03). The "Activity level" was higher in the ASD probands having rs1925608 "CC". Additionally, the score for "Relating to people" was higher in the presence of rs1925575 "TC" genotypes. The gender-based stratified analysis revealed the influence of the variants on a higher number of traits of the female probands. This pilot investigation indicated an influence of LRRTM3 genetic variants on the trait severity of Indian ASD probands.