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TNF-alpha −308G/A and −238G/A polymorphisms and its protein network associated with type 2 diabetes mellitus
- Source :
- Saudi Journal of Biological Sciences, Vol 24, Iss 6, Pp 1195-1203 (2017)
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- Several reports document the role of tumor necrosis factor alpha (TNF-α) 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-α gene in T2DM in the Indian population with bioinformatics analysis of TNF-α 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-α 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-α −308G/A polymorphism. The results obtained were evaluated statistically to determine the significance. By constructing TNF-α 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-α. Through hub analysis of TNF-α 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-α −308G/A, −238G/A were not significantly associated to type 2 diabetes mellitus, but TNF-α −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-α T2DM pathogenesis. Keywords: TNF-α, Type 2 diabetes mellitus, Polymorphism, Genotypes, SNPs, Protein interaction network
- Subjects :
- 0301 basic medicine
Genotypes
030209 endocrinology & metabolism
Single-nucleotide polymorphism
Biology
Bioinformatics
Article
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Diabetes mellitus
Genotype
Type 2 diabetes mellitus
medicine
Polymorphism
lcsh:QH301-705.5
Agricultural and Biological Sciences(all)
Type 2 Diabetes Mellitus
Promoter
medicine.disease
Protein interaction network
030104 developmental biology
lcsh:Biology (General)
TNF-α
Tumor necrosis factor alpha
General Agricultural and Biological Sciences
TCF7L2
SNPs
Subjects
Details
- Language :
- English
- Volume :
- 24
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Saudi Journal of Biological Sciences
- Accession number :
- edsair.doi.dedup.....f76e8b1187cf012f3ad0939f979b52f9