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.
Conclusion: 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.