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.
Keywords: Type 2 diabetes, cytokines, gene-gene interaction, haplotype, pedigree analysis, SNP, north Indian population.
Amylin Replacement With Pramlintide as an Adjunct to Insulin Therapy in Type 1 and Type 2 Diabetes Mellitus: A Physiological Approach Toward Improved Metabolic Control
Current Pharmaceutical Design Non-diabetic Glucose levels and Cancer Mortality: A Literature Review
Current Diabetes Reviews Plasma Phospholipids are Associated with Mild Cognitive Impairment in Type 2 Diabetic Patients
Current Alzheimer Research Urinary Exosomal Lipidomics Reveals Markers for Diabetic Nephropathy
Current Metabolomics Endothelial Dysfunction in Diabetes: From Mechanisms to Therapeutic Targets
Current Medicinal Chemistry Management of Blood Pressure and Heart Rate in Patients with Diabetes Mellitus
Current Pharmaceutical Design Global View on Alzheimer’s Disease and Diabetes Mellitus: Threats, Risks and Treatment Alzheimer’s Disease and Diabetes Mellitus
Current Alzheimer Research Fibrates and Microvascular Complications in Diabetes - Insight from the FIELD Study
Current Pharmaceutical Design Induced Pluripotent Stem Cells as a Model for Accelerated Patient- and Disease-specific Drug Discovery
Current Medicinal Chemistry Glucose Transport Regulators
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Brittle Type 1 Diabetes Mellitus
Current Medicinal Chemistry Protein Misfolding and Aggregation in Alzheimer's Disease and Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets Amyloidogenicity of p53: A Hidden Link Between Protein Misfolding and Cancer
Current Protein & Peptide Science Flavonoids: Cellular and Molecular Mechanism of Action in Glucose Homeostasis
Mini-Reviews in Medicinal Chemistry A Simple High Efficiency Intra-Islet Transduction Protocol Using Lentiviral Vectors
Current Gene Therapy Short and Long Term Effects of a DPP-4 Inhibitor Versus Bedtime NPH Insulin as ADD-ON Therapy in Patients with Type 2 Diabetes
Current Pharmaceutical Design Cardiovascular Risk in Perimenopausal Women
Current Vascular Pharmacology Empagliflozin for Type 2 Diabetes Mellitus: An Overview of Phase 3 Clinical Trials
Current Diabetes Reviews Type 2 Diabetes Mellitus: New Genetic Insights will Lead to New Therapeutics
Current Genomics Food Applications for Flaxseed and its Components: Products and Processing
Recent Patents on Food, Nutrition & Agriculture