Association of ADIPOR2 With Liver Function Tests in Type 2 Diabetic Subjects

Abstract

Objective: Adiponectin protects against liver dysfunction in insulin-resistant states such as obesity and type 2 diabetes (T2DM), but the role of adiponectin receptors in this disorder is largely unknown. We studied whether common single-nucleotide polymorphisms (SNPs) in ADIPOR1 and ADIPOR2 are associated with liver function tests (LFTs) in human subjects with various degrees of insulin resistance. Methods and Procedures: Serum alanine (ALT) and aspartate (AST) aminotransferases, homeostasis model assessment of insulin resistance (HOMA-IR), -8503 G/A (rs6666089) and +5843 C/T (rs1342387) SNPs in ADIPOR1, -64,241 T/G (rs1029629) and +33447 C/T (rs1044471) SNPs in ADIPOR2 were assessed in 700 white subjects from a population-based study. Results: In nondiabetic subjects, the at-risk alleles for the common -64,241 T/G and +33447 C/T SNPs in ADIPOR2 were associated with increased circulating adiponectin (P < 0.05 to P < 0.005), but not with LFT. Conversely, in T2DM subjects (who are at risk for liver dysfunction), the same alleles were associated with increased serum ALT and AST (P < 0.05 to P < 0.0001), but not with circulating adiponectin. No significant associations with these parameters were evident for the common -8503 G/A and +5843 C/T SNPs in ADIPOR1. In a replication study, the -64,241 T/G and +33447 C/T SNPs in ADIPOR2 were associated with ALT and AST (P < 0.05 to P < 0.0001) in pooled obese and T2DM subjects. Discussion: Common SNPs in ADIPOR2 are associated with LFT in T2DM subjects, which suggests a possible role of this receptor in liver dysfunction associated with insulin resistance.

Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts

“…SNPs in genes encoding peroxisome proliferator-activated receptor g coactivator 1 a (28), adiponutrin (29), CLOCK transcription factor (30), PPARD (10), and upstream transcription factor 1 (13) have recently been shown to be related to variation in liver fat content in humans. Two polymorphisms in ADIPOR2 (K64,241 T/G and C33447 C/T) were shown to be associated with serum ALT and AST concentrations in patients with type 2 diabetes, but not in non-diabetic subjects (31). In addition, loci on chromosomes 10 (CPN1-ERLIN1-CHUK) and 22 (PNPLA3-SAMM50) were associated with ALT concentrations, and a locus on chromosome 12 (HNF1A) with gGT concentrations (32) in individuals from the general population.…”

Probiotic Mechanisms Affecting Glucose Homeostasis: A Scoping Review

“…The role of the major adiponectin receptor gene, i.e., adiponectin receptor 2 (AdipoR2), has been linked to insulin resistance and type 2 diabetes, where it plays a crucial role in glucose and lipid metabolism, inflammation and oxidative stress [ 143 ]. In a study on rats [ 109 ], the probiotic Lactobacillus casei Zhang also increased the expression of AdipoR2 in fat cells.…”

Associations of adiponectin receptor 2 (AdipoR2) gene polymorphisms and AdipoR2 protein expression levels with the risk of colorectal cancer: A case-control study

“…Furthermore, certain single nucleotide polymorphisms (SNPs) in the AdipoR2 gene, such as rs1342387, rs1063538, rs266729 and rs1862513, may be associated with CRC risk ( 6 , 13 – 15 ). In addition, rs10773989 and rs1044471 in the AdipoR2 gene have been reported to be associated with various types of disease, such as type 2 diabetes, and prostate and gastric cancer ( 16 – 18 ). However, such associations between the SNPs in AdipoR2 and CRC remain controversial ( 19 , 20 ).…”