Genetics
Obesity (2008) 16 10, 2308–2313. doi:10.1038/oby.2008.344
Association of ADIPOR2 With Liver Function Tests in Type 2 Diabetic Subjects
Abel López-Bermejo1,2, Patricia Botas-Cervero3, Francisco Ortega-Delgado1,2,4, Elías Delgado5, Maria M. García-Gil2, Tohru Funahashi6, Wifredo Ricart1,2,4 and José M. Fernández-Real1,2,4
- 1Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Girona, Spain
- 2Girona Institute for Biomedical Research, Girona, Spain
- 3Endocrinology Unit, San Agustín Hospital, Avilés (Asturias), Spain
- 4CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03/010), Santiago de Compostela, Spain
- 5Endocrinology Unit, Asturias Central Hospital, Oviedo (Asturias), Spain
- 6Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, Osaka, Japan
Correspondence: Abel López-Bermejo (uden.alopez@htrueta.scs.es)
Received 20 June 2007; Accepted 14 January 2008; Published online 24 July 2008.
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.
