Investigating the Association between NID۱ Gene SNPs with Mandibular Prognathism: An In silico Study

Class III malocclusion is a special type of jaw deformity that can result mandibularprognathism (MP) [۱]. Genetic factors such as single nucleotide polymorphisms (SNPs) can cause thisprotrusion. Nidogen-۱ is an extracellular glycoprotein encoded by the NID۱ gene and plays a crucialrole in stabilizing, cell adhesion, and mediating cell-matrix interactions. In silico studies can help toidentify effective SNPs in the structure and stability of Nidogen-۱ and to predict their relationship withMP. In this study, missense SNPs of the NID۱ gene and their effects on MP were investigated. At first,all missense SNPs of the NID۱ gene monitored. Missense SNPs with a minor allele frequency (MAF)≥۰.۱ were selected in the NCBI-dbSNP database. The effect of each selected SNPs based on functional,structural, and stability aspects of the protein and mRNA were investigated by twelve online software:SIFT, Polyphen-۲, Meta LR, PantherDB, PROVEAN, I-mutant, iStable, MUpro, FATHMM, RNAsnp,PSIPRED, and GeneMANIA. Analysis of missense SNPs by SIFT, Polyphen-۲, and PantherDB showedthat rs۳۷۳۸۵۳۱ (C>A, Gln۸۰۷His), could be as a deleterious SNP. The prediction of the effects of thisSNP by I-mutant, iStable, MUpro, and PSIPRED also showed substitution of Gln۸۰۷His may decreasethe stability of the protein. Analysis association of NID۱ by GeneMANIA showed that this protein hasa co-expression and Physical Interactions with the heparan sulfate proteoglycan ۲ (HSPG۲), which isknown as Perlecan, with a score of ۰.۰۱۳۳۵۲۸۹۴ [۲]. Perlecan and Nidogen-۱ impact chondrocyte andosteoblast functions [۳]. Given their roles, the co-expression of HSPG۲ and NID۱ may haveimplications for MP. Furthermore, rs۳۷۳۸۵۳۱ has been associated with structural changes in mRNAwith a significant P-value, potentially emphasizing the translation of NID۱. Based on this study, theNID۱ gene plays an important role in MP development and rs۳۷۳۸۵۳۱ is expected to be effective inmandibular growth.

کلیدواژه ها:

In silico analysis ، Mandibular prognathism ، Missense SNPs ، Nidogen-۱ ، Perlecan