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

Narayana Swamy A, Valasala H, Kamma S - Avicenna J Med Biotechnol (2015 Jul-Sep)

Bottom Line: A total of 58 nonsynonymous SNPs consisting of 55 missense variations, 3 nonsense variations were found in the ADIPOQ gene.Totally, 10 variants out of 55 missense variants were predicted to be both deleterious and reduce protein stability.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, K L University, Vaddeswaram, India.

ABSTRACT

Background: 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.

Methods: 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.

Result: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Graphical representation of deleterious variations.
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Figure 1: Graphical representation of deleterious variations.

Mentions: In PolyPhen-2 analysis, 26 (47.8%) of the 55 variants were predicted to be probably damaging, and the others were predicted to be benign or possibly damaging, whereas in SIFT, 18 variants (32.7%) were predicted to be damaging, and others were predicted to be tolerated. By PROVEAN analysis, 27 variants (49.1%) were predicted to be deleterious, but the others were neutral (Figure 1). Among the above, 16 (29%) common ADIPOQ gene variants, namely, c.133G>C (p. Gly45Arg), c.140C>T (p.Pro47Leu), c.143G>A (p. Gly48Asp), c.161G>T (p.Gly54Val), c.163C>T (p.Arg 55Cys), c.223G>T (p.Gly75Cys), c.250G>A (p.Gly 84Arg), c.268G>A (p.Gly90Ser), c.334C>T (p.Arg 112Cys) c.335G>C (p.Arg112Leu), c.335G>T (p.Arg 112Pro), c.353G>A (p.Gly118Glu), c.425A>T (p.His 142Leu), c.593C>T (p.Ser198Phe), c.595G>A (p.Gly 199Ser), andc.626A>G (p.Asp209Gly) were found.


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

Narayana Swamy A, Valasala H, Kamma S - Avicenna J Med Biotechnol (2015 Jul-Sep)

Graphical representation of deleterious variations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508335&req=5

Figure 1: Graphical representation of deleterious variations.
Mentions: In PolyPhen-2 analysis, 26 (47.8%) of the 55 variants were predicted to be probably damaging, and the others were predicted to be benign or possibly damaging, whereas in SIFT, 18 variants (32.7%) were predicted to be damaging, and others were predicted to be tolerated. By PROVEAN analysis, 27 variants (49.1%) were predicted to be deleterious, but the others were neutral (Figure 1). Among the above, 16 (29%) common ADIPOQ gene variants, namely, c.133G>C (p. Gly45Arg), c.140C>T (p.Pro47Leu), c.143G>A (p. Gly48Asp), c.161G>T (p.Gly54Val), c.163C>T (p.Arg 55Cys), c.223G>T (p.Gly75Cys), c.250G>A (p.Gly 84Arg), c.268G>A (p.Gly90Ser), c.334C>T (p.Arg 112Cys) c.335G>C (p.Arg112Leu), c.335G>T (p.Arg 112Pro), c.353G>A (p.Gly118Glu), c.425A>T (p.His 142Leu), c.593C>T (p.Ser198Phe), c.595G>A (p.Gly 199Ser), andc.626A>G (p.Asp209Gly) were found.

Bottom Line: A total of 58 nonsynonymous SNPs consisting of 55 missense variations, 3 nonsense variations were found in the ADIPOQ gene.Totally, 10 variants out of 55 missense variants were predicted to be both deleterious and reduce protein stability.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, K L University, Vaddeswaram, India.

ABSTRACT

Background: 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.

Methods: 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.

Result: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus