The association of adiponectin serum level and ADIPOQ +45 T/G and ADIPOR1 −106 A/G gene polymorphisms with diabetic nephropathy in type 2 DM

Abstract

Adiponectin encoded by ADIPOQ, gene (adiponectin, C1Q and Collagen Domain-Containing) is an adipocyte-derived protein, plays a major role in mediating insulin sensitivity, and lower plasma adiponectin concentration has been linked to microangiopathies in type 2 diabetes mellitus (DM). It has been hypothesized that blood adiponectin concentration may reflect the extent of kidney damage in diabetic patients. Our aim was to study genetic polymorphisms in adiponectin genes (ADIPOQ +45 T/G and adiponectin receptor 1 (ADIPOR1) −106 A/G) and the serum level of adiponectin in type 2 DM and to correlate this with the stages of diabetic nephropathy. Forty-eight patients with type 2 DM were recruited from Internal Medicine Department and Nephrology Outpatient Clinic in Kasr El Aini Hospital, Cairo University, from April 2011 until March 2012. They were divided into normoalbuminuric (nonnephropathic), n = 17; and nephropathic group, n = 31; who were further subdivided into microalbuminuric, macroalbuminuric, and end-stage renal disease groups. They were compared to ten healthy control subjects. Blood urea, creatinine, HbA1c, and adiponectin were measured. ADIPOQ +45 T/G and ADIPOR1 −106 A/G gene polymorphisms were analyzed by PCR RFLP. Serum adiponectin was significantly lower in nephropathic group versus nonnephropathic and control group (P = 0.026) with the lowest level in macroalbuminuric group (P < 0.001). Serum urea, blood glucose, HbA1c, and duration of diabetes were found to be independent predictors of adiponectin level, r 2 = 0.59. In case of ADIPOQ, most of the cases carried the TT genotype, and there was absence of GG genotype in both cases and control. The ADIPOR1 gene polymorphism was strongly associated with type 2 DM and diabetic nephropathy. The G allele of ADIPOR1 was found to be a risk factor for type 2 DM with OR 3.1 (95 % confidence interval 1.1–8.5), P = 0.028. This evidence highlights the role of ADIPOR1 in the pathogenesis of diabetic nephropathy and type 2 diabetes (T2D), suggesting AdipoR1 as a promising target for the treatment of T2D patients, particularly those who have microalbuminuria. Also, adiponectin serum level is a biomarker for kidney disease and may be targeted for prevention and treatment.