Determination of the effects of high-risk deleterious snps in some genes associated with parkinson's disease by in silico methods

Parkinson's disease, which is a neurodegenerative disease, has a very complex etiology. In individuals with a genetic predisposition to certain environmental factors, it is conceivable that the environmental factors they are exposed to lead to the clinic. However, it is known that genetic factors alone play a significant role in the etiology of the disease. Mutations and polymorphisms are among the genetic factors specified for Parkinson's disease. It was aimed to determine the possible effects of single nucleotide polymorphisms (SNPs) in SNCA, CD38, GBA, LRP10, EIF4G1, VPS35, PLA2G6, PINK1, LRRK2, UQCR1, MMRN1 genes on the function, structure, stabilization, and evolutionary conservation of proteins using various bioinformatics tools. For theMMRN1 gene, it was determined that rs1046993 (L982S), rs61734879 (N1075K), rs1432306000 (8G274), rs147438202 (R1057M) rs147438202 (G16R), rs147451161 (R1227L), rs148141919 (Q394R), rs149261966 (S1155R), rs189386556 (S414P), rs199716183 (Y1097H), rs200526047 (P651H), rs201006967 (P1140L), rs201761344 (N1084S), rs369001499 (M1100K), rs370732997 (D726Y), rs373754512 (D225G), rs374677318 (C592Y), rs376506594 (C211Y) polymorphisms may have damaging effects.It was determined that rs201911056 (R276C), rs145869559 (G312S), rs191821836 (R165S), rs200354059 (R378C) variants for theUQCR1 gene and rs4640000 (P1262A), rs33995463 (L119P), rs150050676 (N246H) variants for the LRRK2 gene might be pathogenic.It was predicted that the identified missense SNPs may cause structural and functional changes in proteins involved in various biological processes and, as a result of these changes, adversely affect biological processes. In this study, the missense SNPs identified as pathogenic were evaluated as risk factors for Parkinson's disease. The potential use of these pathogenic missense SNPs as biomarkers may provide a basis for diagnosis and treatment. The results of this studyneed to be confirmed by further in vitro and in vivo studies in Parkinson's disease.