Chemerin, Visfatin, Omentin-1 and Their Gene Polymorphisms Associated With Diabetes Associated Chronic Kidney Disease

Abstract

Background The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly, especially in India, mainly because of the increasing prevalence of obesity and unhealthy lifestyles. These trigger an increase in the prevalence of macrovascular (cardiovascular) and microvascular (nephropathy, neuropathy, and retinopathy) complications of T2DM. One such microvascular complication of T2DM is diabetes associated-chronic kidney disease (CKD). Estimates suggest that almost 40% of T2DM patients develop diabetes associated-CKD, which not only affects their normal lifestyle but also reduces their life expectancy by 16 years. The current study aimed to provide two pro-inflammatory markers, Chemerin and Visfatin, and one anti-inflammatory marker, Omentin-1, which may help in diagnosis, prognosis and treatment planning in diabetes-associated CKD patients. Estimates suggest that multiple environmental and genetic factors contribute to diabetes-associated CKD. However, the exact link between genetic variation and diabetes associated-CKD is still a field of research. This research study is designed to contribute towards the finding of a link between genetic variation and diabetes-associated CKD by determining the association of rs17173608 polymorphism of the RARRES2 (Chemerin) gene, rs9770242 and rs1319501 polymorphisms of the NAMPT (Visfatin) gene, rs2274907 and rs2274908 polymorphisms of the Omentin-1 gene to the susceptibility of diabetes-associated CKD. Methods The case-control study was conducted at tertiary care center, south India. The total sample size of the study was calculated to be 180 (n = 180), which further divided into 3 equal groups two case groups: sixty participants with T2DM (Group-I), sixty participants with diabetes-associated CKD (Group-II), and one control group with sixty age (25–65years) and sex-matched normal healthy participants. Serum Chemerin, Visfatin, and Omentin-1 levels were quantified and compared among all the groups. Regression analysis was conducted to find the association of these inflammatory markers and their gene polymorphism with the development of CKD among T2DM partcipants. Findings Elevated serum Chemerin in participants with T2DM [3168.90 (1985.78, 6822.02)]ng/ml, with further elevated levels in participants with diabetes-associated CKD [5571.70 (2645.05, 14072.00)]ng/ml was observed as compared to normal healthy participants [1465.85 (638.58, 2574.25)]ng/ml. Similarly, elevated serum Visfatin in participants with T2DM [38.34 (32.31, 72.73)]ng/ml, with further elevated levels in participants with diabetes-associated CKD [46.61 (31.45, 131.07)]ng/ml was observed as compared to normal healthy participants 14.22(8.865, 18.619)]ng/ml. However, decreased serum Omentin-1 in participants with T2DM [0.92 (0.86, 0.97)]ng/ml and in participants with diabetes-associated CKD [0.83 (0.60, 0.92)]ng/ml was observed, as compared to normal healthy participants [1.23 ± (1.09–1.48)]ng/ml. Regression analysis revealed that increase in Visfatin levels increase the risk of development of CKD among T2DM as well as decrease Visfatin levels increase the risk of development of CKD among T2DM. Area Under the curve (AUC) for these inflammatory marker was found to be 0.953, suggesting the good validity of these markers in predicting the development of risk of CKD among T2DM. Chemerin rs17173608 and Visfatin rs9770242, rs1319501 gene polymorphism were found to be associated with increase risk of development CKD among T2DM patients. Interpretation The above findings clearly indicate that estimation of serum Chemerin, Visfatin, and Omentin-1 levels and their specific polymorphism may have significant role in diagnosis and prognosis of diabetes associated complications like CKD.