title: TNF-α (g.-308 G > A) and ADIPOQ (g. + 45 T > G) gene polymorphisms in type 2 diabetes and microvascular complications in the region of Punjab (North-West India).
abstract: OBJECTIVE
  The present study aims to examine the association of tumor necrosis factor-α (TNF-α) g.-308 G > A and adiponectin (ADIPOQ) g. + 45 T > G gene polymorphisms in type 2 diabetes (T2D) and its microvascular complications diabetic retinopathy (DR) and diabetic nephropathy (DN).
  
  
  METHODS
  A total of 672 individuals were analysed from the North-West population of Punjab. Genotyping was accomplished by a combination of allele specific amplification refractory mutation system and restriction digestion for TNF-α g. - 308 G > A and ADIPOQ g. + 45 T > G polymorphisms, respectively. Further, in silico modeling was done to predict secondary structure of mRNA for g. + 45 T > G polymorphism in the ADIPOQ gene by RNA fold.
  
  
  RESULTS
  The minor allele frequency observed in the controls for the TNF-α G > A and ADIPOQ T > G polymorphisms were 0.07 and 0.10, respectively. The results show no significant association with TNF-α g. - 308 G > A polymorphism in T2D as well as in any of the microvascular complication. However, the ADIPOQ g. + 45 T > G polymorphism shows significant association in T2D (p = 0.048) and DR (p = 0.001) but in DN patients, no association was observed. Interactive analysis revealed that the two polymorphisms jointly conferred a 1.45-fold risk towards the occurrence of T2D [p = 0.031; OR = 1.45 (1.03-2.05)]. In the secondary structure of mRNA, slight free energy change was observed between the wild ( - 1370.28 kcal/mol) and variant allele (-1369.08 kcal/mol).
  
  
  CONCLUSIONS
  Our results indicated a higher risk of T2D and DR in the background of ADIPOQ TT genotype. Further, the ADIPOQ g. + 45 T > G and TNF-α g. - 308 G > A polymorphisms jointly give 1.45-fold risk towards T2D.
authors.affiliation: Department of Human Genetics, Guru Nanak Dev University , Amritsar, Punjab , India .
authors.forename: Ruhi
authors.initials: R
authors.lastname: Sikka
authors.forename: Priyanka
authors.initials: P
authors.lastname: Raina
authors.forename: Kawaljit
authors.initials: K
authors.lastname: Matharoo
authors.forename: Khushdeep
authors.initials: K
authors.lastname: Bandesh
authors.forename: Rajan
authors.initials: R
authors.lastname: Bhatia
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: A J S
authors.initials: AJ
authors.lastname: Bhanwer
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D060005:Genotyping Techniques; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: Diabetic nephropathy; North–West Indian population; SNP; diabetic retinopathy; type 2 diabetes