Abstract
ObjectivePrevious genome-wide association studies have indicated an association between CDH13 genotypes and adiponectin levels. In this study, we used mediation analysis to assess the statistical association between CDH13 locus variants and adiponectin levels, metabolic syndrome, and related metabolic phenotypes.Methods and resultsA sample population of 530 Taiwanese participants was enrolled. Four CDH13 gene variants in the promoter and intron 1 regions were genotyped. After adjustment for clinical covariates, the CDH13 genotypes/haplotypes exhibited an association with the adiponectin levels (lowest P = 1.95 × 10−11 for rs4783244 and lowest P = 3.78 × 10−13 for haplotype ATTT). Significant correlations were observed between the adiponectin levels and the various metabolic syndrome-related phenotypes (all P ≤ 0.005). After further adjustment for the adiponectin levels, participants with a minor allele of rs12051272 revealed a considerable association with a more favorable metabolic profile, including higher insulin sensitivity, high-density lipoprotein cholesterol levels, lower diastolic blood pressure, circulating levels of fasting plasma glucose, and triglycerides, and as a lower risk of metabolic syndrome (all P < 0.05). The mediation analysis further revealed a suppression effect of the adiponectin levels on the association between CDH13 genotypes and metabolic syndrome and its related phenotypes (Sobel test; all P < 0.001).ConclusionThe genetic polymorphisms at the CDH13 locus independently affect the adiponectin levels, whereas the adiponectin levels exhibit a suppressive effect on the association between CDH13 locus variants and various metabolic phenotypes and metabolic syndrome. In addition, these results provide further evidence of the association between the CDH13 gene variants and the risks of metabolic syndrome and atherosclerotic cardiovascular disease.
Highlights
Adiponectin is one of the most abundant gene products expressed in adipose tissues and plays a crucial role in the metabolic regulation of obesity, insulin sensitivity, and atherosclerosis [1]
The genetic polymorphisms at the CDH13 locus independently affect the adiponectin levels, whereas the adiponectin levels exhibit a suppressive effect on the association between CDH13 locus variants and various metabolic phenotypes and metabolic syndrome
CDH13 genotypes represent rs12051272, which was analyzed in the dominant models, α: unstandardized coefficient for the association between the CDH13 genetic variants and log adiponectin levels; β: unstandardized coefficient for the association between adiponectin and metabolic phenotypes, such as diastolic blood pressure (BP), glucose levels, QUICKI, high-density lipoprotein (HDL) cholesterol, triglyceride levels and metabolic syndrome
Summary
Adiponectin is one of the most abundant gene products expressed in adipose tissues and plays a crucial role in the metabolic regulation of obesity, insulin sensitivity, and atherosclerosis [1]. Several studies have indicated many metabolic actions of adiponectin, such as antidiabetic, antiinflammatory, and antiatherosclerotic actions [2]. Decreased levels of plasma adiponectin have been associated with an increased risk of obesity, metabolic syndrome, and atherosclerotic cardiovascular disease [4,5,6,7]. Genetic factors have been suggested to regulate adiponectin levels, as demonstrated by the twin study [8], family study [9], and genomewide linkage scans [10], which indicated moderate to high estimates of heritability (30%–70%) [11]. A recent family-based study reported a shared heritability between adiponectin levels and metabolic syndrome [12]
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