In silico Evaluation of Nonsynonymous Single Nucleotide Polymorphisms in the ADIPOQ Gene Associated with Diabetes, Obesity, and Inflammation

The human ADIPOQ gene encodes adiponectin protein hormone, which is involved in regulating glucose levels as well as fatty acid breakdown. It is exclusively produced by adipose tissue and abundantly present in the circulation, with concentration of around 0.01% of total serum proteins, with important effect on metabolism. Most deleterious nonsynonymous single nucleotide polymorphisms in the coding region of the ADIPOQ gene were investigated using SNP databases, and detected nonsynonymous variants were analyzed in silico from the standpoint of relevant protein function and stability by using SIFT, PolyPhen-2, PROVEAN and MUpro, I-Mutant2.0 tools, respectively. A total of 58 nonsynonymous SNPs consisting of 55 missense variations, 3 nonsense variations were found in the ADIPOQ gene. Next, 14 of the 55 missense variants were predicted to be damaging or deleterious by three different software programs (PolyPhen-2, SIFT, and PROVEAN), and 38 of them were predicted to be less stable (I-Mutant 2.0 and MUpro software). Totally, 10 variants out of 55 missense variants were predicted to be both deleterious and reduce protein stability. Additionally, 3 nonsense variants were predicted to produce a truncated ADIPOQ protein. RMSD and total energy were calculated for 4 nsSNPs out of 10 nsSNPs which were both deleterious and showed a decrease in protein stability. rs144526209 has high root-mean-square deviation (RMSD) and lower total energy value compared to the native modeled structure. It was concluded that this nsSNP, potentially functional and polymorphic in the ADIPOQ gene, might be associated with diabetes, obesity, and inflammation.