title: Genetic variation in CDH13 is associated with lower plasma adiponectin levels but greater adiponectin sensitivity in East Asian populations.
abstract: Variants in the CDH13 gene have been identified as determinants of blood levels of adiponectin, an insulin-sensitizing adipokine. However, their association with other metabolic risk factors remains unclear. We examined variants at CDH13 in relation to total and high-molecular-weight (HMW) adiponectin using data from a genome-wide association study performed in 2,434 Singaporean Chinese with replication in up to 3,290 Japanese and 1,610 Koreans. The top signal rs4783244 in CDH13 showed strong associations with total adiponectin (standardized β [β] = -0.34, 95% CI -0.38 to -0.30, P = 2.0 × 10(-70)), HMW adiponectin (β = -0.40, 95% CI -0.43 to -0.36, P = 1.1 × 10(-117)), and the HMW-to-total adiponectin ratio (β = -0.44, 95% CI -0.49 to -0.40, P = 3.2 × 10(-83)). In the replication study, this single nucleotide polymorphism explained 4.1% of total and 6.5% of HMW adiponectin levels. No association was observed between rs4783244 and metabolic traits associated with insulin resistance before adjustment for HMW adiponectin levels. After adjustment for HMW adiponectin levels, the minor allele was associated with lower BMI (β = -0.15, 95% CI -0.19 to -0.11, P = 3.5 × 10(-14)), homeostasis model assessment-insulin resistance index (β = -0.16, 95% CI -0.20 to -0.12, P = 9.2 × 10(-16)), and triglycerides (β = -0.16, 95% CI -0.19 to -0.12, P = 1.3 × 10(-16)) and with higher HDL (β = 0.16, 95% CI 0.12 to 0.19, P = 2.1 × 10(-17)). CDH13 variants strongly influence plasma total and HMW adiponectin levels in East Asian populations but appear to alter adiponectin sensitivity, resulting in better metabolic health than expected based on circulating adiponectin levels.
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
authors.forename: He
authors.initials: H
authors.lastname: Gao
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Michiya
authors.initials: M
authors.lastname: Igase
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Kawamoto
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lee
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Rick Twee-Hee
authors.initials: RT
authors.lastname: Ong
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onuma
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Osawa
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Yik Ying
authors.initials: YY
authors.lastname: Teo
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012846:Singapore
chemical_list: D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin