Your browser doesn't support javascript.
loading
CDH13 promoter SNPs with pleiotropic effect on cardiometabolic parameters represent methylation QTLs.
Putku, Margus; Kals, Mart; Inno, Rain; Kasela, Silva; Org, Elin; Kozich, Viktor; Milani, Lili; Laan, Maris.
Afiliação
  • Putku M; Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Riia St. 23, 51010, Tartu, Estonia.
Hum Genet ; 134(3): 291-303, 2015 Mar.
Article em En | MEDLINE | ID: mdl-25543204
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); ß = 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), ß = -1,841.9 ng/mL) and rs77068073 (P = 2.67 × 10(-4), ß = -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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pressão Sanguínea / Caderinas / Regiões Promotoras Genéticas / Metilação de DNA Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Genet Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estônia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pressão Sanguínea / Caderinas / Regiões Promotoras Genéticas / Metilação de DNA Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Genet Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estônia