title: Cytokine Gene Variants as Predictors of Type 2 Diabetes Mellitus.
abstract: BACKGROUND
  Diabetes is the third widespread after heart disease and cancer. We have investigated genetic polymorphisms in cytokine genes viz. IL-4, IL-1Ra, IL-1β, IL-18, IL-6, TNF-α, IL-10 and ADIPOQ. The aim of study was to investigate the haplotypes, gene-gene interactions and their role in determining individual susceptibility to T2DM of family members with diabetic history.
  
  
  METHODS
  Haplotype analysis of 2 SNPs each in IL-6 and adiponectin genes showing Pairwise Linkage disequilibrium (LD) was done by SHEsis software. Logistic regression was used to study various combinations of gene-gene interactions.
  
  
  RESULTS
  The TCGT* set of allele combination appeared to increase the disease risk upto 2 times while TATG* upto 51.4 times when four SNPs are taken together viz. IL-1β-511 C/T, IL-18-607 A/C, ADIPOQ1 +45 G/T and ADIPOQ2 +10211 T/G. Interaction of SNPs in eight genes showed one highly significant combination of alleles, TCGAGCTT* which increased the risk of T2DM upto 7.4 times while CAGAGCGT* allele combination increased the risk upto 4 times.
  
  
  CONCLUSIONS
  During pedigree analysis in six families with four SNPs, it was interesting to note that susceptible 'AC' genotype of IL-18-607 A/C was frequent in diabetic individuals in almost all families. Moreover, when checked for the presence of risk haplotypes it was observed that TCGT* and TATG* sets of allele combinations were present in most of the diabetic individuals. Individuals with certain abnormal biochemical parameters but not yet diagnosed for T2DM carried the risk genotype or haplotype. This suggested that individuals carrying risk genotypes/haplotypes might be susceptible to T2DM and develop the disease in the future.
authors.affiliation: Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh - 226007, India.
authors.forename: Madhukar
authors.initials: M
authors.lastname: Saxena
authors.affiliation: Department of Physiology, King George`s Medical University, Lucknow, Uttar Pradesh -226003, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Srivastava
authors.affiliation: Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh - 226007, India.
authors.forename: Monisha
authors.initials: M
authors.lastname: Banerjee
mesh_terms: D052242:Adiponectin / Q000235:genetics; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004843:Epistasis, Genetic; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D016207:Cytokines; C508609:IL10 protein, human; C508585:IL1B protein, human; C508590:IL1R1 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D053573:Receptors, Interleukin-1 Type I; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4
keywords: SNP; Type 2 diabetes; cytokines; gene-gene interaction; haplotype; north Indian population; pedigree analysis.