Análise in silico do polimorfismo rs1803909 do gene ANXA2 expresso em monócitos de sangue periférico e a sua relação com a osteoporose humana

In silico analysis of the rs1803909 polymorphysis of the ANXA2 gene expressed in peripheral blood monocytes and its association with human osteoporosis

Abstract

Osteoporosis is considered the most common bone disease in the world, and is characterized by low bone mass, consequent degradation of the microstructure of its tissue and reduction of its resistance. Thus, this study aimed to evaluate the possible morphofunctional and protein stability changes due to Tyrosine amino acid changes by a Histidine at position 269, as well as to correlate with the physiological function of the protein and its probable link to human osteoporosis. Through an in silico analysis based on information available in the NCBI dbSNP (amino acid change and position) and UNIPROT (sequence in the protein) databases. The impacts of the Y269H modification were analyzed from the SIFT, Align GVGD, SNAP and PROVEAN tools (function and structure), and PolyPhen-2 (nature of the change). In addition, the MuPRO tool (stability change in the protein) was also used. From the in silico analysis of the rs1803909 polymorphism, functional alteration was demonstrated (SIFT tool, Score= 0). As well as, it was estimated that amino acid exchanges may be related to harmful alterations (PolyPhen-2, Score= 0.993) and associated to modifications in protein function (PROVEAN, Score= -4.015). In addition, structural (Align GVGD, Score= 83.33, Class C65) and functional (SNAP, Score= 57) impacts were observed. Complementarily, decreased protein stability resulting from the Y269H alteration was observed by the MuPRO tool, ΔΔG= -1.6731749. However, morphofunctional alterations may be linked to damaging processes and the elevation and/or decrease of protein stability, thus hindering its action. Furthermore, understanding the morphofunctional and stability changes of rs1803909 may aid in the search for early diagnostic genetic and molecular markers for osteoporosis in humans.