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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 protein stability analysis.
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Figure 2: Graphical representation of protein stability analysis.

Mentions: Changes in the protein stability of missense variants were examined using I-Mutant 2.0 and MUpro software (Figure 2). In I-Mutant 2.0 prediction, 47 (85.4%) of 55 variants and in case of MUpro analysis, 41 (74.5%) variants were predicted to decrease protein stability. A total of 37 variants (67.2%) out of the 55 missense variants, including 10 out of 16 common damaging or deleterious variants namely c.133G>C (p. Gly45Arg), c.143G>A (p.Gly48Asp), c.163C>T (p. Arg55Cys), c.223G>T (p.Gly75Cys), c.250G>A (p. Gly84Arg), c.268G>A (p.Gly90Ser), c.334C>T (p. Arg112Cys) c.335G>C (p.Arg112Leu), c.595G>A (p. Gly199Ser), and c.626A>G (p.Asp209Gly) as determined using PolyPhen-2, SIFT, and PROVEAN software applications, were predicted to be less stable using both the I-Mutant 2.0 and the MUpro software.


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 protein stability analysis.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Graphical representation of protein stability analysis.
Mentions: Changes in the protein stability of missense variants were examined using I-Mutant 2.0 and MUpro software (Figure 2). In I-Mutant 2.0 prediction, 47 (85.4%) of 55 variants and in case of MUpro analysis, 41 (74.5%) variants were predicted to decrease protein stability. A total of 37 variants (67.2%) out of the 55 missense variants, including 10 out of 16 common damaging or deleterious variants namely c.133G>C (p. Gly45Arg), c.143G>A (p.Gly48Asp), c.163C>T (p. Arg55Cys), c.223G>T (p.Gly75Cys), c.250G>A (p. Gly84Arg), c.268G>A (p.Gly90Ser), c.334C>T (p. Arg112Cys) c.335G>C (p.Arg112Leu), c.595G>A (p. Gly199Ser), and c.626A>G (p.Asp209Gly) as determined using PolyPhen-2, SIFT, and PROVEAN software applications, were predicted to be less stable using both the I-Mutant 2.0 and the MUpro software.

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