Genetic Association of ENPP1 (rs1044498K/Q), TCF7L2 (rs1225572G/T) and GYS1 (rs8103451A1/A2) Gene Variants with Type 2 Diabetes Mellitus (T2DM) and Obesity in North Indian Punjabi Population

Background: To investigate the genetic association of the ENPP1 (rs1044498K/Q), TCF7L2 (rs1225572G/T) and GYS1 (rs8103451A1/A2) gene variants with type 2 diabetes (T2DM) and obesity in the north Indian Punjabi Population.

Methods: In the case-control approach, a total of 500 unrelated participants, 250 T2DM cases and 250 controls were recruited. All the known T2DM patients were recruited from the different clinical centers in Amritsar district in Punjab. Anthropometric and physiometric measurements were taken on each individual using standard techniques and tools. The variants were screened by polymerase chain reaction-restriction fragment length polymorphism.

Results: Most of the significant clinical variables have higher means in obese individuals than non-obese individuals. In the non-diabetic control group, individuals with wild genotypes demonstrated similar results, except for the random plasma glucose levels among the GG genotype carriers of polymorphism rs1225572. Additionally, variations in the age of onset of disease and duration of disease were noted for the A1A1 genotype of polymorphism rs8103451. Among the three risk genotypes of three gene variants, the means of weight and BMI for KQ+QQ, GT+TT and A1A2+A2A2 genotypes; waist circumference, hip circumference, supra-iliac skinfold and systolic blood pressure for KQ+QQ and GT+TT genotypes; waist-hip ratio, supra-iliac skinfold, biceps skinfold for KQ+QQ genotypes and pulse pressure for GT+TT genotype have shown statistically significant differences (p<0.001) between obese and non-obese type 2 diabetes mellitus (T2DM) individuals. In the present analysis, the association of twenty such quantitative variables related to obesity has been assessed among T2DM patients and non-diabetic controls. From the above extensive comparison, it was found that BMI, WC and HC for pooled subjects are the significant covariates for obese T2DM patients irrespective of wild and risk genotypes for all the three SNPs as compared to non-obese T2DM patients. The same trend has also been observed in obese and non-obese non-diabetics.

Conclusion: The data replicated the association of T2DM with related obesity such as body mass index, waist circumference, hip circumference, systolic and diastolic blood pressures which unravels an identifiable mechanism behind T2DM and measures of obesity in the north Indian population regardless of the genotypic combinations.