Role of Leptin Receptor (LEPR) Gene Polymorphisms and Haplotypes in Susceptibility to Hepatocellular Carcinoma in Subjects with Chronic Hepatitis B Virus Infection

Abstract

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. 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. The genotype frequencies of Lys109Arg and Gln223Arg differed significantly between HCC and non-HCC 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 109Lys-656Lys-223Gln and 109Lys-656Asn-223Gln haplotypes had protective effects against HCC development. None of these polymorphisms were related to the clinicopathologic features of HCC. The Lys109Arg and Gln223Arg polymorphisms of the LEPR gene are associated with susceptibility 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.