Novel locus FER is associated with serum HMW adiponectin levels

Diabetes. 2011 Aug;60(8):2197-201. doi: 10.2337/db10-1645. Epub 2011 Jun 23.

Abstract

Objective: High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels.

Research design and methods: We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses' Health Study (NHS) (N = 1,591). The single nucleotide polymorphisms (SNPs) identified in the GWAS analysis were replicated in an independent cohort of Europeans (N = 626). We examined the associations of the identified variations with diabetes risk and metabolic syndrome.

Results: We identified a novel locus near the FER gene (5q21) at a genome-wide significance level, best represented by SNP rs10447248 (P = 4.69 × 10(-8)). We also confirmed that variations near the adiponectin-encoding ADIPOQ locus (3q27) were related to serum HMW adiponectin levels. In addition, we found that FER SNP rs10447248 was related to HDL cholesterol levels (P = 0.009); ADIPOQ variation was associated with fasting glucose (P = 0.04), HDL cholesterol (P = 0.04), and a metabolic syndrome score (P = 0.002).

Conclusions: Our results suggest that different loci may be involved in regulation of circulating HMW adiponectin levels and provide novel insight into the mechanisms that affect HMW adiponectin homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood*
  • Adiponectin / genetics*
  • Adult
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Metabolic Syndrome / genetics
  • Middle Aged
  • Molecular Weight
  • Polymorphism, Single Nucleotide

Substances

  • Adiponectin