Research Papers:

Effect modification by region in the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced CK elevation

Shanqun Jiang _, Scott A. Venners, Kang Li, Yi-Hsiang Hsu, Justin Weinstock, Yanfeng Zou, Faming Pan and Xiping Xu

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Oncotarget. 2017; 8:107565-107576. https://doi.org/10.18632/oncotarget.22506

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Shanqun Jiang1,2, Scott A. Venners3, Kang Li1, Yi-Hsiang Hsu4,5, Justin Weinstock6, Yanfeng Zou7, Faming Pan7 and Xiping Xu2,8

1School of Life Sciences, Anhui University, Hefei, China

2Institute of Biomedicine, Anhui Medical University, Hefei, China

3Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada

4Institute for Aging Research, HSL and Harvard Medical School, Boston, MA, USA

5Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, USA

6Department of Statistics, University of Virginia, Charlottesville, VA, USA

7Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China

8Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, IL, USA

Correspondence to:

Shanqun Jiang, email: [email protected]

Keywords: LEP G2548A; LEPR Q223R; creatine kinase; hyperlipidemia; simvastatin

Received: August 24, 2017     Accepted: October 28, 2017     Published: November 18, 2017


We investigated the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced creatine kinase (CK) elevation among Chinese patients with hyperlipidemia. A total of587 enrolled individuals were treated with 20 mg/d oral simvastatin for 8 consecutive weeks. Genotyping of LEP G2548A and LEPR Q223R were conducted using PCR-RFLP. Multiple regression analyses showed that, in the Dongzhi region only, patients carrying the LEP AA genotype had a significantly greater increase in CK levels compared to those carrying the AG+GG genotypes after four weeks (P = 0.004) and eight weeks (P < 0.001) consecutive simvastatin treatment. Patients were further divided into three groups based on the tertiles of the CK distribution. Compared to subjects in the lowest tertile of CK elevation, the adjusted relative odds of having the AG+GG genotypes among subjects in the highest tertile was 0.5 (95% CI, 0.3 to 0.7) and 0.4 (95% CI, 0.2 to 0.6) after the fourth and eighth weeks, respectively. The interaction terms between the Beijing or Dongzhi region and the LEP GA+AA genotypes were marginally significant for CK elevation at the fourth week (P = 0.057) and significant for CK elevation at the eighth week (P = 0.002). The adverse effect of the LEP G2548A polymorphism on increasing CK levels may be dependent on the environmental milieu. It suggests that lifestyle interventions might offset the side effects of simvastatin therapy among those with genetic susceptibility. Further research is needed to identify specific individual-level factors for clinical practice that modify the effect of genotype.

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