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Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people

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Abstract

Recent genome-wide association studies reported that GCKR rs780094 polymorphism is associated with elevated fasting serum triglyceride levels and elevated levels of C-reactive protein (CRP). There are a ample of data on the association between circulating triglyceride, CRP concentrations and risk of non-alcoholic fatty liver (NAFLD). To determine whether the GCKR rs780094 polymorphism contributes to the development of non-alcoholic fatty liver, a case–control study was performed in 903 Chinese subjects. Among study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis I°, 90 with steatosis hepatis II° and 28 with steatosis hepatis III°) and 467 controls were genotyped by using TaqMan allelic discrimination assays. We confirmed the association of GCKR rs780094 with NAFLD in Chinese people (OR = 1.607, 95% CI 1.139–2.271, P [dom] = 7.2 × 10−3). In this study, polymorphism in GCKR rs780094 was not significantly associated with the degree of fatty infiltration of the liver. In addition, the T-allele of GCKR rs780094 was significantly associated with increasing fasting triglyceride (P [add] = 3.8 × 10−4) and CRP (P [add] = 2.9 × 10−4) concentrations after adjusting for age, gender, and BMI. The association with NAFLD remained significant after adjustment for triglyceride, while adjustment for CRP abolished the association. Genetic variation in GCKR gene rs780094 polymorphism contributes to the risk of NAFLD in Chinese people. The effect of genotype on NAFLD is probably mediated through chronic low-grade systemic inflammation rather than through dislipidemia.

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Acknowledgments

The authors thank all the subjects for participating. The authors also thank Zhihong Yang, Qin Li, Wenbai Zhou, Yuwei Zhang, Min He, Shuo Zhang, Xiaocheng Feng and Xiaolong Zhao for their assistance in the laboratory measurements and the epidemiological survey. This study was supported by the National High Technology Research and Development Program (“863”Program) of China (2009AA022704), the National Natural Science Foundation of China (330670999, 30711120573, 3030770854), Shanghai Science and Technology Commission (08dj1400605, 08JC1403200, 09DZ1950200), China Postdoctoral Science Foundation (20080440078) and Shanghai Postdoctoral Scientific Program (09R21411600).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Huashan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai Medical School, Fudan University, 12# Wulumuqi Middle Road, Shanghai, 200040, China

    Zhen Yang, Jie Wen, Xiaoming Tao, Bin Lu, Yanping Du, Mei Wang, Xuanchun Wang, Weiwei Zhang, Wei Gong & Renming Hu

  2. Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, CRC Malmö University Hospital, Lund University Diabetes Center, 205 02, Malmö, Sweden

    Charlotte Ling

  3. Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai No. 6 People Hospital, Shanghai Jiaotong University, Shanghai, 200233, China

    Songhua Wu

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  1. Zhen Yang
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Correspondence to Renming Hu.

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Yang, Z., Wen, J., Tao, X. et al. Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people. Mol Biol Rep 38, 1145–1150 (2011). https://doi.org/10.1007/s11033-010-0212-1

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  • DOI: https://doi.org/10.1007/s11033-010-0212-1

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