The “GG” genotype of rs26802 variant in the ghrelin gene is a potential protective factor against nonalcoholic fatty liver disease

Abstract

Background Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease worldwide. Considering the powerful association between NAFLD, insulin resistance (IR) and obesity, as well as the key role of ghrelin in these metabolic disorders, we hypothesized that some single nucleotide polymorphisms (SNPs) of the ghrelin (GHRL) and ghrelin receptor (GHSR) genes might be associated with NAFLD. Methods We conducted a case-control retrospective study of 150 cases with biopsy-proven NAFLD and 155 controls. The diagnosis of NAFLD was established before the start of the genotyping process. All the 305 subjects were genotyped for GHRL SNP rs26802 or -501T>G and GHSR SNP rs572169 or Arg159Arg using the PCR-RFLP method. Results The GHRL rs26802 “GG” genotype compared with the “TT” genotype and “TT+TG” genotype appears to be a marker of decreased NAFLD susceptibility even after adjustment for confounding factors (P = 0.006; OR = 0.14, 95% CI = 0.03–0.56 and P = 0.003; OR = 0.16, 95% CI = 0.05–0.53, respectively). However, we observed no significant difference in genotype or allele frequencies between the cases and controls for GHSR SNP rs572169. Conclusions These findings proposed, for the first time, that the GHRL rs26802 “GG” genotype has a protective effect against NAFLD. Nonetheless, this observation warrants further investigations in other populations.

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) .…”