Adiponectin Genetic Variant and Expression Coupled with Lipid Peroxidation Reveal New Signatures in Diabetic Dyslipidemia.

Abstract

Increasing burden of non-communicable diseases like diabetes and cardiovascular disorders has made the global health scenario more challenging. Dyslipidemia in diabetes is a compounding risk factor for cardiovascular diseases, but there is dearth of identifying appropriate signatures to address this issue. The protein, adiponectin, is actively involved in regulating glucose levels as well as fatty acid breakdown playing crucial role in dyslipidemia and vascular complications. To identify the underlying genetic and molecular profile of adiponectin metabolic pathway in diabetic dyslipidemia and to correlate it with known biochemical and oxidative stress parameters of T2DM, we performed a case-control study in a total 264 individuals belonging to three categories such as diabetes with dyslipidemia (n = 88), diabetes without dyslipidemia (n = 86) and normal healthy controls (n = 90). Expression of adiponectin (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) were measured in visceral and subcutaneous adipose tissues. A significant downregulated expression of ADIPOQ and its receptors in adipose tissues and PBMCs were linked with diabetic dyslipidemic condition. A multiple linear regression followed by MDR analysis implicated the elevated plasma malondialdehyde and decreased adiponectin level to be correlated with diabetic dyslipidemia. More interestingly, two single nucleotide polymorphisms of ADIPOQ (rs2241766 and rs1501299) were genetically associated with the risk of developing dyslipidemia. Other important biochemical factors found to be increased in diabetic dyslipidemic conditions included plasma C-reactive protein and 4-hydroxynonenal adducts. Our results explore, a complex interplay of genetic and biochemical parameters in diabetic dyslipidemia which is significant from the perspective of risk stratification and novel therapeutic strategy development.