A Correlation Study Between Neuroligin-4 Gene And Nonspecific Mental Retardation In The Chinese Children In The Qinba Mountains Region

Mental Retardation(MR)is one of human psychosis illnesses,which characterized by little intelligence and significant limitation in the social and practical adaptive skills.The incidence of MR is estimated currently around 1-3%in some countries and regions among children of 18 years old or younger.Two groups have been defined as nonspecific forms(NSMR),in which MR is the only clinical manifestation,and syndromic forms(SMR),in which MR is associated with recognizable physical signs such as skeletal abnormalities or dysmorphic facial features.MR is brought by many causes,including trachoma,infection,trauma, dystrophy,toxicosis,cerebral palsy,or birth complications and genetic factors. Genetic etiologies are found in approximately two-thirds of mentally retarded cases.Neuroligin-4(NL4)belongs to a family of brain neurone-specific membrane proteins.They are particularly abundant in the postsynaptic membrane of glutamatergic synapses and have been localized to the postsynaptic membranes of excitatory synapses.The NLGN4 gene is located on chromosome Xp22.3,harbors six exons,which belongs to neuroligin family.NLGN4 encode 816 amino acids,which are composed of NL4.NL4 is indispensable to proper synapse maturation and brain function.Loss-of-function mutations in the human gene NLGN4 cause autism and MR.The case-control method was used to study the association between nonspecific mental retardation(NSMR)and genetic variants of neuroligin-4 gene(NLGN4).Five single nucleotide polymorphisms(SNPs:rs5916271,rs7049300,rs6638575, rs3810686 and rs1882260)were analyzed by PCR-RFLP/SSCP method in the NLGN4.Individual SNP analysis showed significant differences at SNPs rs3810686 and rs1882260 for allele frequency when NSMR cases and controls(OR=1.589,95% CI=1.035-2.438,χ~2=4.53,df=1,p=0.033;OR=2.050,95%CI=1.211-3.470,χ~2 =7.38,df=1,p=0.007,respectively)were compared.Further haplotype analysis indicated that there were two haplotype sets,rs3810686-rs1882260 and rs6638575-rs3810686-rs1882260,which showed statistical differences between NSMR cases and controls(χ~2=7.9,df=3,global p=0.047;χ~2=12.91,df=5, global p=0.024,respectively).The results suggested a positive association between the genetic variants of the NLGN4 and NSMR in the Chinese children from Qinba Mountains Region.