Role of Leptin Receptor ( LEPR ) Gene Polymorphisms and Haplotypes in Susceptibility to Hepatocellular Carcinoma in Subj
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ORIGINAL RESEARCH ARTICLE
Role of Leptin Receptor (LEPR) Gene Polymorphisms and Haplotypes in Susceptibility to Hepatocellular Carcinoma in Subjects with Chronic Hepatitis B Virus Infection Zhen Li • Weitang Yuan • Shijie Ning • Jie Li • Wenlong Zhai • Shuijun Zhang
Published online: 23 October 2012 Ó Springer International Publishing Switzerland 2012
Abstract Aim The reported association of the leptin receptor (LEPR) protein with hepatocellular carcinoma (HCC) carcinogenesis prompted us to evaluate whether genetic polymorphisms of the LEPR gene affect susceptibility to HCC and its clinicopathologic characteristics. Methods A total of 417 subjects who were diagnosed with HCC and 551 age- and sex-matched subjects without HCC were enrolled in this study. All subjects had chronic hepatitis B virus (HBV) infection. Three single nucleotide polymorphisms (SNPs) of the LEPR gene were determined. Results The genotype frequencies of Lys109Arg and Gln223Arg differed significantly between HCC and nonHCC subjects (both p \ 0.001). For the Lys109Arg polymorphism, HCC subjects had a higher prevalence of 109Arg/Arg than non-HCC subjects. The 109Arg/Arg carriers had a significantly higher adjusted risk of HCC than the 109Lys/Lys carriers. For the Gln223Arg polymorphism, subjects with the 223Arg/Arg genotype had a significantly higher risk of HCC than those with the 223Gln/Gln genotype. The Lys656Asn SNP did not affect the HCC risk. Haplotype analyses showed that subjects with 109Lys-656Lys-223Arg and 109Arg-656Asn-223Arg haplotypes had an increased HCC risk, while the 109Lys656Lys-223Gln and 109Lys-656Asn-223Gln haplotypes had protective effects against HCC development. None of these polymorphisms were related to the clinicopathologic features of HCC. Conclusion The Lys109Arg and Gln223Arg polymorphisms of the LEPR gene are associated with susceptibility Z. Li (&) W. Yuan S. Ning J. Li W. Zhai S. Zhang Department of General Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China e-mail: [email protected]
to HCC but not with its clinicopathologic features. These polymorphisms may represent genetic markers for the risk of HCC in the context of chronic HBV infection.
1 Introduction Hepatocellular carcinoma (HCC) is one of the common causes of cancer-related death worldwide [1, 2]. It has been estimated that 80 % of HCC worldwide is etiologically associated with hepatitis B virus (HBV) infection [3, 4]. China has high incidence rates of chronic viral hepatitis, cirrhosis, and HCC [5]. Research efforts in recent years have focused on investigating the cellular, molecular, and genetic pathways involved in the progression of HCC. As a result, some genetic variants have been reported as diagnostic and prognostic markers for HCC [6–8]. Leptin receptor (LEPR) is a single transmembrane protein belonging to the superfamily of cytokine receptors, which mediates the physiologic action of leptin (LEP). The interaction between LEP and LEPR plays an important role in various physiologic processes, inclu
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