Identification of Susceptibility Variants in ADIPOR1 Gene Associated with Type 2 Diabetes, Coronary Artery Disease and the Comorbidity of Type 2 Diabetes and Coronary Artery Disease

OBJECTIVE Adiponectin receptor 1 (encoded by ADIPOR1) is one of the major adiponectin receptors, and plays an important role in glucose and lipid metabolism. However, few studies have reported simultaneous associations between ADIPOR1 variants and type 2 diabetes (T2D), coronary artery disease (CAD) and T2D with CAD. Based on the "common soil" hypothesis, we investigated whether ADIPOR1 polymorphisms contributed to the etiology of T2D, CAD, or T2D with CAD in a Northern Han Chinese population. METHODS Our multi-disease comparison study enrolled 657 subjects, including 165 with T2D, 173 with CAD, 174 with both T2D and CAD (T2D+CAD), and 145 local healthy controls. Six ADIPOR1 single nucleotide polymorphisms (SNPs) were genotyped and their association with disease risk was analyzed. RESULTS Multi-case-control comparison identified two ADIPOR1 variants: rs3737884-G, which was simultaneously associated with an increased risk of T2D, CAD, and T2D+CAD (P-value range, 9.80×10(-5)-6.30×10(-4); odds ratio (OR) range: 1.96-2.42) and 16850797-C, which was separately associated with T2D and T2D+CAD (P-value range: 0.007-0.014; OR range: 1.71-1.77). The risk genotypes of both rs3737884 and 16850797 were consistently associated with common metabolic phenotypes in all three diseases (P-value range: 4.81×10(-42)-0.001). We observed an increase in the genetic dose-dependent cumulative risk with increasing risk allele numbers in T2D, CAD and T2D+CAD (P trend from 1.35×10(-5)-0.002). CONCLUSIONS Our results suggest that ADIPOR1 risk polymorphisms are a strong candidate for the "common soil" hypothesis and could partially contribute to disease susceptibility to T2D, CAD, and T2D with CAD in the Northern Han Chinese population.