Genetic Variation in CDH13 Is Associated With Lower Plasma Adiponectin Levels but Greater Adiponectin Sensitivity in East Asian Populations
- He Gao1,2,3,
- Yu-Mi Kim4,
- Peng Chen1,
- Michiya Igase5,
- Ryuichi Kawamoto6,
- Mi Kyung Kim7,
- Katsuhiko Kohara5,
- Jeannette Lee1,
- Tetsuro Miki5,
- Rick Twee-Hee Ong1,
- Hiroshi Onuma8,
- Haruhiko Osawa8,
- Xueling Sim9,10,
- Yik Ying Teo1,2,11,
- Yasuharu Tabara12,
- E Shyong Tai1,13,14 and
- Rob M. van Dam1,2,13⇑
- 1Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
- 2National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
- 3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- 4Department of Preventive Medicine, Dong-A University College of Medicine, Busan, South Korea
- 5Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
- 6Department of Community Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
- 7Department of Preventive Medicine, HanYang University College of Medicine, Seoul, South Korea
- 8Department of Molecular and Genetic Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
- 9Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan
- 10Centre for Molecular Epidemiology, National University of Singapore, Singapore
- 11Department of Statistics and Applied Probability, National University of Singapore, Singapore
- 12Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- 13Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
- 14Duke-National University of Singapore Graduate Medical School, National University of Singapore, Singapore
- Corresponding author: Rob M. van Dam, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0129/-/DC1.
Y.T., E.S.T., and R.M.v.D. jointly directed this work.
- Received January 24, 2013.
- Accepted September 1, 2013.
- © 2013 by the American Diabetes Association.
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