title: Association of CDH13 genotypes/haplotypes with circulating adiponectin levels, metabolic syndrome, and related metabolic phenotypes: the role of the suppression effect.
abstract: OBJECTIVE
  Previous 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.
  
  
  RESULTS
  A 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).
  
  
  CONCLUSIONS
  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. 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.
authors: Graduate Institute of Medical Sciences, Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.
authors: Ming-Sheng
authors: MS
authors: Teng
authors: The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Lung-An
authors: LA
authors: Hsu
authors: Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan; Department of Life Science, Chinese Culture University, Taipei, Taiwan.
authors: Semon
authors: S
authors: Wu
authors: Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors: Yu-Chen
authors: YC
authors: Sun
authors: Graduate Institute of Medical Sciences, Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Shu-Hui
authors: SH
authors: Juan
authors: The Division of Cardiology, Department of Internal Medicine and Cardiovascular Medical Center, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors: Yu-Lin
authors: YL
authors: Ko
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D000483:Alleles; D015820:Cadherins / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan
chemical_list: D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin; D007328:Insulin; D002784:Cholesterol; D005947:Glucose