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

Abstract

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a growing problem and the commonest cause of chronic liver disease throughout the world. Given the strong association between NAFLD and insulin resistance and obesity, as well as the central role of ghrelin in these metabolic disorders, we explored whether ghrelin (GHRL) and ghrelin receptor (GHSR) gene polymorphisms were associated with susceptibility to NAFLD.
 Methods: In this case-control retrospective study which was conducted between April 2010 and July 2013, GHRL (rs696217 or Leu72Met) and GHSR (rs2922126) gene polymorphisms were genotyped in 153 cases with biopsy-proven NAFLD and 157 controls using the polymerase chain reaction - restriction fragment length polymorphism method.
 Results: The GHRL rs696217 “GT+TT” genotype or “GT” genotype compared with the “GG” genotype occurred less frequently in the patients with NAFLD than the controls and the differences remained significant after adjustment for confounding factors such as age and body mass index (p=0.018; OR=0.35, 95%CI: 0.14–0.84 and p=0.046; OR=0.40, 95%CI: 0.16–0.98, respectively). Furthermore, the GHRL rs696217 ‘T’ allele compared with ‘G’ allele was significantly underrepresented in the cases (p=0.007; OR=0.33, 95%CI: 0.15-0.76). Nevertheless, no significant difference was found for GHSR rs2922126 gene polymorphism.
 Conclusions: Our findings suggested, for the first time, that the GHRL rs696217 or Leu72Met “GT+TT” genotype and “GT” genotype compared with “GG” genotype, as well as the “T” or Met72 allele compared with “G” or Leu72 allele had a protective effect for NAFLD susceptibility. However, other studies are required to confirm these findings.

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

“…Additionally, higher levels of AG, but not UAG, were observed in higher stages of fibrosis [ 78 ]. Further evidencing the role of ghrelin in NAFLD, recent case-control retrospective studies of biopsy-proven NAFLD patients suggested that the Leu72Met (rs696217 G > T) polymorphism and the “GG” genotype of rs26802 variant in the ghrelin gene have a protective effect against NAFLD [ 79 , 80 ].…”

Resistin Gene Polymorphism and Nonalcoholic Fatty Liver Disease Risk

“…The increased levels of liver enzymes are also much lower in the NAFLD patients without IR than those with IR (10) . Previous reports have also shown that in addition to insulin (INS), insulin receptor (INSR), insulin receptor substrates (IRSs), insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) are all involved in IR and insulin signaling pathway (11) ; and it is interesting that significant associations have been found between NAFLD risk and INSR, IRS2, IGF1, and GHRL gene polymorphisms (12)(13)(14)(15)(16)(17) .…”