Association of Ghrelin Gene Polymorphisms and Serum Ghrelin Levels with the Risk of Hepatitis B Virus-Related Liver Diseases in a Chinese Population

Abstract

BackgroundThe functions of ghrelin (GHRL) include anti-inflammatory effects, reduction of the fibrogenic response, protection of liver tissue, and regulation of cell proliferation. Genetic variations in the GHRL gene may play an important role in the development of chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we investigated whether GHRL gene polymorphisms and its serum levels are associated with hepatitis B virus (HBV)-related diseases risk in a Chinese population.Methods176 patients with CHB, 106 patients with HBV-related LC, 151 patients with HBV-related HCC, and 167 healthy controls were recruited in the study. Genotyping of GHRL rs26311, rs27647, rs696217, and rs34911341 polymorphisms were determined with the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA).ResultsBinary logistic regression analyses adjusting for gender and age revealed that a significant increased risk of LC was found in the GHRL rs26311 GC genotype and combined GC+CC genotypes when compared with the GG genotype (GC vs. GG: OR = 1.671, 95% CI = 1.013–2.757, P = 0.044; GC+CC vs. GG: OR = 1.674, 95% CI = 1.040–2.696, P = 0.034). In subgroup analysis by gender, binary logistic regression analyses adjusting for age showed that the GHRL rs26311 C allele and combined GC+CC genotypes were associated with a significantly increased risk to LC in males (C vs. G OR = 1.416, 95% CI = 1.017–1.972, P = 0.040; GC+CC vs. GG: OR = 1.729, 95% CI = 1.019–2.933, P = 0.042). In addition, we found significant decreased serum GHRL levels in LC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26311 polymorphism with serum GHRL levels in LC patients.ConclusionsThese observations suggest that the GHRL rs26311 polymorphism is associated with an increased risk to HBV-related LC, especially in men. We also found an inverse association of serum GHRL levels with LC.

Contributions of polymorphisms in miR146a, miR196a, and miR499 to the development of hepatocellular carcinoma

“…The etiology of the disease has been widely studied, and previous research has demonstrated that many environmental and lifestyle factors, such as hepatitis B/C virus infection, aflatoxins, long-term alcohol consumption and liver cirrhosis (Nguyen et al, 2009;Liu et al, 2012;Niu et al, 2016). Previous studies have demonstrated that many genetic variations contribute to the risk of developing hepatocellular carcinoma, including C-reactive protein, Holliday junction recognition protein (HJURP), epidermal growth factor 61A/G, and Ghrelin and FasL genes (Lao et al, 2015;Shen et al, 2015b;Zhang et al, 2015a;Huang et al, 2016;Khalifa et al, 2016).…”

The Leu72Met (rs696217 G>T) Polymorphism of the Ghrelin Gene Might Be a Protective Factor for Nonalcoholic Fatty Liver Disease

“…Additionally, it has been suggested that other GHRL gene polymorphisms are significantly associated with circulating levels of glucose [49], insulin [46], metabolic syndrome [50], hypertension [51], and hepatocellular carcinoma [52]. And finally, serum levels of ghrelin decrease in the patients with either liver advanced fibrosis or liver cirrhosis and GHRL gene variants influence the progression of liver fibrosis and liver cirrhosis [53,54]. The other possible hypothesis linking the rs696217 polymorphism with NAFLD risk is through linkage disequilibrium.…”

FABP1 Polymorphisms Contribute to Hepatocellular Carcinoma Susceptibility in Chinese Population with Liver Cirrhosis: A Case-Control Study

“…SNPs were reported to be involved in HBV-related liver diseases. Zhang X et al observed that, in healthy controls, the ghrelin rs26311 GC+CC genotype increased the risk of LC in contrast to the GG genotype ( P = 0.034), especially in males ( P = 0.042) 25 . Healthy individuals carrying toll-like receptor 3 (TLR3) rs3775290 TT genotype had a decreased risk for CHB, HBV-related LC and HCC 26 .…”