PMID- 32064572
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2001-1326 (Print)
IS  - 2001-1326 (Electronic)
IS  - 2001-1326 (Linking)
VI  - 9
IP  - 1
DP  - 2020 Feb 17
TI  - Computational determination of human PPARG gene: SNPs and prediction of their 
      effect on protein functions of diabetic patients.
PG  - 7
LID - 10.1186/s40169-020-0258-1 [doi]
LID - 7
AB  - BACKGROUND: The Peroxisome proliferator-activated receptor gamma gene (PPARG), 
      encodes a member of the peroxisome-activated receptor subfamily of nuclear 
      receptors. PPARs form heterodimers with retinoid X receptors (RXRs) which 
      regulate transcription of various genes. Three subtypes of PPARs are known: 
      PPAR-alpha, PPAR-delta and PPAR-gamma. The protein encoded by this gene is 
      PPAR-gamma which is a regulator of adipocyte differentiation. PPARG-gamma has 
      been implicated in the pathology of numerous diseases including obesity, 
      diabetes, atherosclerosis and cancer. AIM: This study aimed to perform insilico 
      analysis to predict the effects that can be imposed by SNPs reported in PPARG 
      gene. METHODOLOGY: This gene was investigated in NCBI database 
      (http://www.ncbi.nlm.nih.gov/) during the year 2016 and the SNPs in coding region 
      (exonal SNPs) that are non-synonymous (ns SNPs) were analyzed by computational 
      softwares. SIFT, Polyphen, I-Mutant and PHD-SNP softwares). SIFT was used to 
      filter the deleterious SNPs, Polyphen was used to determine the degree of 
      pathogenicity, I-Mutant was used to determine the effect of mutation on protein 
      stability while PHD-SNP software was used to investigate the effect of mutation 
      on protein function. Furthermore, Structural and functional analysis of ns SNPs 
      was also studied using Project HOPE software and modeling was conducted by 
      Chimera. RESULTS: A total of 34,035 SNPs from NCBI, were found, 21,235 of them 
      were found in Homo sapiens, 134 in coding non synonymous (missense) and 89 were 
      synonymous. Only SNPs present in coding regions were selected for analysis. Out 
      of 12 deleterious SNPs sorted by SIFT, 10 were predicted by Polyphen to be 
      probably damaging with PISC score = 1 and only two were benign. All these 10 
      double positive SNPs were disease related as predicted by PHD-SNPs and revealed 
      decreased stability indicated by I-Mutant. CONCLUSION: Based on the findings of 
      this study, it can be concluded that the deleterious ns SNPs (rs72551364 and 
      rs121909244SNPs) of PPARG are important candidates for the cause of different 
      types of human diseases including diabetes mellitus.
FAU - Mustafa, Howeida Abdullah
AU  - Mustafa HA
AUID- ORCID: 0000-0001-7554-2937
AD  - Department of Molecular Biology and Bioinformatics, College of Veterinary 
      Medicine, University of Bahri, Khartoum, Sudan. howeida.mustafa@gmail.com.
AD  - Department of Biochemistry, Faculty of Veterinary Medicine, University of 
      Khartoum, Khartoum, Sudan. howeida.mustafa@gmail.com.
FAU - Albkrye, Afraa Mohamed Suliman
AU  - Albkrye AMS
AD  - Department of Molecular Biology and Bioinformatics, College of Veterinary 
      Medicine, University of Bahri, Khartoum, Sudan.
FAU - AbdAlla, Buthiena Mohamed
AU  - AbdAlla BM
AD  - Department of Molecular Biology and Bioinformatics, College of Veterinary 
      Medicine, University of Bahri, Khartoum, Sudan.
AD  - Department of Biochemistry, College of Applied and Industrial Science, University 
      of Bahri, Bahri, Sudan.
FAU - Khair, Mona AbdelRahman Mohammed
AU  - Khair MAM
AD  - Department of Molecular Biology and Bioinformatics, College of Veterinary 
      Medicine, University of Bahri, Khartoum, Sudan.
FAU - Abdelwahid, Nidal
AU  - Abdelwahid N
AD  - Department of Molecular Biology and Bioinformatics, College of Veterinary 
      Medicine, University of Bahri, Khartoum, Sudan.
FAU - Elnasri, Hind Abdelaziz
AU  - Elnasri HA
AD  - Department of Molecular Biology and Bioinformatics, College of Veterinary 
      Medicine, University of Bahri, Khartoum, Sudan.
LA  - eng
PT  - Journal Article
DEP - 20200217
PL  - United States
TA  - Clin Transl Med
JT  - Clinical and translational medicine
JID - 101597971
PMC - PMC7024687
OTO - NOTNLM
OT  - Diabetes insilico
OT  - PPARG
OT  - Polyphen
OT  - SIFT
OT  - SNP
COIS- The authors declare that they have no competing interests.
EDAT- 2020/02/18 06:00
MHDA- 2020/02/18 06:01
PMCR- 2020/02/17
CRDT- 2020/02/18 06:00
PHST- 2019/05/23 00:00 [received]
PHST- 2020/01/07 00:00 [accepted]
PHST- 2020/02/18 06:00 [entrez]
PHST- 2020/02/18 06:00 [pubmed]
PHST- 2020/02/18 06:01 [medline]
PHST- 2020/02/17 00:00 [pmc-release]
AID - 10.1186/s40169-020-0258-1 [pii]
AID - 258 [pii]
AID - 10.1186/s40169-020-0258-1 [doi]
PST - epublish
SO  - Clin Transl Med. 2020 Feb 17;9(1):7. doi: 10.1186/s40169-020-0258-1.