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Journal of Lipid Research, Vol. 50, 1479-1486, July 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans

Ying Wu^2,*, Huaixing Li^2,*, Ruth J. F. Loos^1,, Qibin Qi^*, Frank B. Hu, Yong Liu^* and Xu Lin^1,*

^* Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
Department of Nutrition, Harvard School of Public Health, Boston, MA
² Y. Wu and H. Li contributed equally to this work.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of three tables.

This study was funded by the National Natural Science Foundation of China (Grant 30571562); the Knowledge Innovation Program Pilot Project of the Chinese Academy of Sciences (KSCX2-YW-R-73); the National Basic Research Program of China (973 Program 2006CB503902); the Major Projects of Knowledge Innovation Program (KSCX2-YW-R-116 and KSCX1-YW-02); and the Shanghai-Unilever Research Development Fund (CH-2006-0941).

Published, JLR Papers in Press, March 14, 2009.

¹ To whom correspondence should be addressed. e-mail: xlin{at}sibs.ac.cn (X.L.) or rjfl2{at}medschl.cam.ac.uk (R.J.F.L.)

We previously found that plasma RBP4 levels were strongly associated with metabolic syndrome components. This study aimed to determine whether RBP4 variants are associated with the metabolic syndrome components and plasma RBP4 levels, and to investigate whether the associations between plasma RBP4 and the metabolic syndrome components are causal. Five tagSNPs were tested for their associations with plasma RBP4 levels and metabolic syndrome components in a population-based sample of 3,210 Chinese Hans. A possible causal relationship between plasma RBP4 levels and hypertriglyceridemia was explored by Mendelian randomization. Plasma RBP4 levels were significantly associated with rs10882273 (βz –0.10SD[–0.17, –0.03], P = 0.0050), rs3758538 (βz –0.13SD[–0.24, –0.02], P = 0.0249) in all participants, and with rs17108993 in Shanghai participants (βz –0.19SD[–0.32, –0.05], P = 0.0061). The single nucleotide polymorphism (SNP) rs3758538 was significantly associated with hypertriglyceridemia (OR 0.62[0.45–0.85], P = 0.0026) and triglycerides (βz –0.19SD[–0.30, –0.07], P = 0.001) in all participants. In Mendelian randomization analysis, the observed effect size of association between rs3758538 and hypertriglyceridemia was different from the expected effect size (P = 0.0213). This is the first study to show that the RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans. However, results of Mendelian randomization do not support the hypothesis that RBP4 levels are causally related to hypertriglyceridemia risk.

Supplementary key words Mendelian randomization • SNP

Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; LD, linkage disequilibrium; MAF, minor allele frequency; OR, odds ratio; RBP4, retinol-binding protein 4; SBP, systolic blood pressure; SNP, single nucleotide polymorphism

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