Abstract
ObjectiveAdiponectin 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.MethodsOur 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.ResultsMulti-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).ConclusionsOur 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.
Highlights
Coronary artery disease (CAD), type 2 diabetes (T2D), and T2D with CAD are multifactorial diseases in which hereditary and environmental factors both contribute to their etiology
Research based on animal models has shown that ADIPOR1 overexpression can augment the biological effects of adiponectin [3], whereas ADIPOR1 knockout leads to increased insulin resistance (IR) and endogenous glucose production [4], suggesting a correlation between ADIPOR1 expression and adiponectin activity [5]
Each single nucleotide polymorphisms (SNPs) conformed to Hardy-Weinberg equilibrium (HWE) (P.0.05) in healthy controls, similar to that reported for Han Chinese in Beijing (HCB) and Southern Han Chinese (CHS) in HapMap or Ensembl databases, but different from those reported for Utah residents with Northern and Western European ancestries from the CEPH collection (CEU) (Table S4)
Summary
Coronary artery disease (CAD), type 2 diabetes (T2D), and T2D with CAD are multifactorial diseases in which hereditary and environmental factors both contribute to their etiology. These diseases may have a common pathogenesis based on the ‘‘common soil’’ hypothesis in which diabetes and cardiovascular disease share common antecedents [1]. Research based on animal models has shown that ADIPOR1 overexpression can augment the biological effects of adiponectin [3], whereas ADIPOR1 knockout leads to increased insulin resistance (IR) and endogenous glucose production [4], suggesting a correlation between ADIPOR1 expression and adiponectin activity [5]. Wang et al showed that down-regulated ADIPOR1 signaling was the underlying mechanism for increased foam cell formation and accelerated cardiovascular disease in diabetic subjects [6]
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