PMID- 28855812
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1319-562X (Print)
IS  - 2213-7106 (Electronic)
IS  - 2213-7106 (Linking)
VI  - 24
IP  - 6
DP  - 2017 Sep
TI  - TNF-alpha -308G/A and -238G/A polymorphisms and its protein network associated 
      with type 2 diabetes mellitus.
PG  - 1195-1203
LID - 10.1016/j.sjbs.2016.05.012 [doi]
AB  - Several reports document the role of tumor necrosis factor alpha (TNF-alpha) and 
      lipid metabolism in the context of acute inflammation as a causative factor in 
      obesity-associated insulin resistance and as one of the causative parameter of 
      type 2 diabetes mellitus (T2DM). Our aim was to investigate the association 
      between -308G/A and -238G/A polymorphisms located in the promoter region of the 
      TNF-alpha gene in T2DM in the Indian population with bioinformatics analysis of TNF-alpha 
      protein networking with an aim to find new target sites for the treatment of 
      T2DM. Demographics of 100 diabetes patients and 100 healthy volunteers were 
      collected in a structured proforma and 3 ml blood samples were obtained from the 
      study group, after approval of Institutional Ethics Committee of the hospital 
      (IEC). The information on clinical parameters was obtained from medical records. 
      Genomic DNA was extracted; PCR-RFLP was performed using TNF-alpha primers specific to 
      detect the presence of SNPs. Various bioinformatics tools such as STRING software 
      were used to determine its network with other associated genes. The PCR-RFLP 
      studies showed that among the -238G/A types the GG genotype was 87%, GA genotype 
      was 12% and AA genotype was 1%. Almost a similar pattern of results was obtained 
      with TNF-alpha -308G/A polymorphism. The results obtained were evaluated 
      statistically to determine the significance. By constructing TNF-alpha protein 
      interaction network we could analyze ontology and hubness of the network to 
      identify the networking of this gene which may influence the functioning of other 
      genes in promoting T2DM. We could identify new targets in T2DM which may function 
      in association with TNF-alpha. Through hub analysis of TNF-alpha protein network we have 
      identified three novel proteins RIPK1, BIRC2 and BIRC3 which may contribute to 
      TNF-mediated T2DM pathogenesis. In conclusion, our study indicated that some of 
      the genotypes of TNF-alpha -308G/A, -238G/A were not significantly associated to type 
      2 diabetes mellitus, but TNF-alpha -308G/A polymorphism was reported to be a potent 
      risk factor for diabetes in higher age (>45) groups. Also, the novel hub proteins 
      may serve as new targets against TNF-alpha T2DM pathogenesis.
FAU - Jamil, Kaiser
AU  - Jamil K
AD  - Genetics Department, Bhagwan Mahavir Medical Research Centre, 10-1-1, Mahavir 
      Marg, AC Guards, Hyderabad 500004, Telangana, India.
AD  - Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal 
      Nehru Institute of Advanced Studies (JNIAS), Buddha Bhawan, 6th Floor, M.G. Road, 
      Secunderabad 500003, Telangana, India.
FAU - Jayaraman, Archana
AU  - Jayaraman A
AD  - Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal 
      Nehru Institute of Advanced Studies (JNIAS), Buddha Bhawan, 6th Floor, M.G. Road, 
      Secunderabad 500003, Telangana, India.
FAU - Ahmad, Javeed
AU  - Ahmad J
AD  - Zoology Department, Osmania University, Hyderabad 500007, Telangana, India.
FAU - Joshi, Sindhu
AU  - Joshi S
AD  - Mahavir Hospital and Research Centre, 10-1-1, Mahavir Marg, AC Guards, Hyderabad 
      500004, Telangana, India.
FAU - Yerra, Shiva Kumar
AU  - Yerra SK
AD  - Cardiology Department, Mahavir Hospital and Research Centre, 10-1-1, Mahavir 
      Marg, AC Guards, Hyderabad 500004, Telangana, India.
LA  - eng
PT  - Journal Article
DEP - 20160525
PL  - Saudi Arabia
TA  - Saudi J Biol Sci
JT  - Saudi journal of biological sciences
JID - 101543796
PMC - PMC5562469
OTO - NOTNLM
OT  - Genotypes
OT  - Polymorphism
OT  - Protein interaction network
OT  - SNPs
OT  - TNF-alpha
OT  - Type 2 diabetes mellitus
EDAT- 2017/09/01 06:00
MHDA- 2017/09/01 06:01
PMCR- 2016/05/25
CRDT- 2017/09/01 06:00
PHST- 2015/10/25 00:00 [received]
PHST- 2016/05/01 00:00 [revised]
PHST- 2016/05/15 00:00 [accepted]
PHST- 2017/09/01 06:00 [entrez]
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2017/09/01 06:01 [medline]
PHST- 2016/05/25 00:00 [pmc-release]
AID - S1319-562X(16)30039-0 [pii]
AID - 10.1016/j.sjbs.2016.05.012 [doi]
PST - ppublish
SO  - Saudi J Biol Sci. 2017 Sep;24(6):1195-1203. doi: 10.1016/j.sjbs.2016.05.012. Epub 
      2016 May 25.