Abstract:PurposeAlthough some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes.Materials and MethodsWe included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association betwe… Show more
“…In addition, the mean carotid intima-media thickness (IMT) was significantly associated with rs12444338 ( p =0.02) and rs1048612 ( p =0.02). 22 In this study, genotypes of the SNP rs3865188 were also associated with DBP. Interestingly, we observed lower insulin levels with increased adiponectin levels in statin-treated subjects with the T allele, compared to statin-free groups with the A allele.…”
PurposeAdiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs).Materials and MethodsWe investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment.ResultsGenetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels.ConclusionPlasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.
“…In addition, the mean carotid intima-media thickness (IMT) was significantly associated with rs12444338 ( p =0.02) and rs1048612 ( p =0.02). 22 In this study, genotypes of the SNP rs3865188 were also associated with DBP. Interestingly, we observed lower insulin levels with increased adiponectin levels in statin-treated subjects with the T allele, compared to statin-free groups with the A allele.…”
PurposeAdiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs).Materials and MethodsWe investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment.ResultsGenetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels.ConclusionPlasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.
“…First, rs149740259, an intron variant of cadherin 13 ( CDH13 ), was associated with mean periodontal attachment loss in a GWAS of PD (Teumer et al 2013). This gene was shown to protect vascular endothelial cells from apoptosis due to oxidative stress (Serbanovic-Canic et al 2017), and it was associated with atherosclerosis in a Korean hypertensive population (Lee et al 2013). In the WGHS, women with the same allele demonstrated nominal associations with ever having PD, prevalent PD, and FamHxMI.…”
Periodontal disease (PD) shares common risk factors with cardiovascular disease. Our hypothesis was that having a family history of myocardial infarction (FamHxMI) may be a novel risk factor for PD. Risk assessment based on FamHxMI, conditional on smoking status, was examined given the strong influence of smoking on PD. Exploratory analysis with inflammatory biomarkers and genetic determinants was conducted to understand potential mechanistic links. The Women's Genome Health Study (WGHS) is a prospective cohort of US female health care professionals who provided blood samples at baseline in the Women's Health Study, a 2 × 2 factorial clinical trial investigating vitamin E and aspirin in the prevention of cardiovascular disease and cancer. PD was ascertained via self-report over 12 y of follow-up. Prevalence (3,442 cases), incidence (1,365 cases), and survival analysis of PD were investigated for associations of FamHxMI as well as in strata of FamHxMI by smoking. Kruskal-Wallis, chi-square tests, multivariate regression, and Cox proportional hazard models were used for the analyses. In the WGHS, women with FamHxMI showed higher risk of ever having PD. A particularly high-risk group of having both FamHxMI and smoking at baseline was highlighted in the prevalence and risk of developing PD. PD risk increased according to the following strata: no FamHxMI and nonsmokers (reference), FamHxMI and nonsmokers (hazard ratio [HR] = 1.2, 95% CI = 1.0 to 1.5), smokers without FamHxMI (HR = 1.3, 95% CI = 1.2 to 1.5), and smokers with FamHxMI (HR = 1.5, 95% CI = 1.2 to 1.8). An independent analysis by the dental Atherosclerosis Risk in Communities study ( N = 5,552) identified more severe periodontitis cases among participants in the high-risk group (smokers with FamHxMI). Further examination of interactions among inflammatory biomarkers or genetic exploration with FamHxMI did not explain the risk increase of PD associated with FamHxMI in the WGHS. Future efforts based on an integrative-omics approach may facilitate validation of these findings and suggest a mechanistic link between PD and FamHxMI.
“…Decreased serum adiponectin levels have recently been showed for ADHD patients suggesting its possible involvement in the pathophysiology of ADHD (Mavroconstanti et al 2014 ). SNPs in CDH13 have been associated with total cholesterol and LDL levels (Dong et al 2011 ; Lee et al 2013 ), coronary artery disease (CAD) (Wellcome Trust Case Control Consortium 2007 ), hypertension and blood pressure (Org et al 2009 ; Levy et al 2007 ; Lee et al 2013 ), hyperlipidemia and myocardial infarction (Shia et al 2011 ), metabolic syndrome (Fava et al 2011 ) and preeclampsia (Wan et al 2013 ). Fig.…”
Section: Introductionmentioning
confidence: 99%
“…CAD coronary artery disease, LDL low-density lipoprotein, SBP systolic blood pressure. a Wallace et al ( 2008 ); b Org et al ( 2009 ), Fava et al ( 2011 ), Wan et al ( 2013 ); c Jee et al ( 2010 ); d Jee et al ( 2010 ), Wu et al ( 2010 ), Jo et al ( 2012 ); e Jee et al ( 2010 ), Chung et al ( 2011 ); f Lee et al ( 2013 ); g Chung et al ( 2011 ), Morisaki et al ( 2012 ), Gao et al ( 2013 ), Uetani et al ( 2014 ); h Morisaki et al ( 2012 ), Dastani et al ( 2012 ); i Dastani et al ( 2012 ); j Lee et al ( 2013 ); k Wellcome Trust Case Control Consortium ( 2007 ); l Ling et al ( 2009 ); m Levy et al ( 2007 ) …”
CDH13 encodes T-cadherin, a receptor for high molecular weight (HMW) adiponectin and low-density lipoprotein, promoting proliferation and migration of endothelial cells. Genome-wide association studies have mapped multiple variants in CDH13 associated with cardiometabolic traits (CMT) with variable effects across studies. We hypothesized that this heterogeneity might reflect interplay with DNA methylation within the region. Resequencing and EpiTYPER™ assay were applied for the HYPertension in ESTonia/Coronary Artery Disease in Czech (HYPEST/CADCZ; n = 358) samples to identify CDH13 promoter SNPs acting as methylation Quantitative Trait Loci (meQTLs) and to investigate their associations with CMT. In silico data were extracted from genome-wide DNA methylation and genotype datasets of the population-based sample Estonian Genome Center of the University of Tartu (EGCUT; n = 165). HYPEST–CADCZ meta-analysis identified a rare variant rs113460564 as highly significant meQTL for a 134-bp distant CpG site (P = 5.90 × 10−6; β = 3.19 %). Four common SNPs (rs12443878, rs12444338, rs62040565, rs8060301) exhibited effect on methylation level of up to 3 neighboring CpG sites in both datasets. The strongest association was detected in EGCUT between rs8060301 and cg09415485 (false discovery rate corrected P value = 1.89 × 10−30). Simultaneously, rs8060301 showed association with diastolic blood pressure, serum high-density lipoprotein and HMW adiponectin (P < 0.005). Novel strong associations were identified between rare CDH13 promoter meQTLs (minor allele frequency <5 %) and HMW adiponectin: rs2239857 (P = 5.50 × 10−5, β = −1,841.9 ng/mL) and rs77068073 (P = 2.67 × 10−4, β = −2,484.4 ng/mL). Our study shows conclusively that CDH13 promoter harbors meQTLs associated with CMTs. It paves the way to deeper understanding of the interplay between DNA variation and methylation in susceptibility to common diseases.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-014-1521-6) contains supplementary material, which is available to authorized users.
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