Novel Locus FER Is Associated With Serum HMW Adiponectin Levels

  1. Frank B. Hu1,2,5
  1. 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  2. 2Department of Medicine, Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  3. 3Research Unit of Diabetes and Endocrine Diseases, IRCCS “Casa Sollievo della Sofferenza,” San Giovanni Rotondo, Italy
  4. 4Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
  5. 5Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  1. Corresponding author: Lu Qi, nhlqi{at}channing.harvard.edu.

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.

Footnotes

  • Received November 29, 2010.
  • Accepted May 16, 2011.

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  1. Diabetes vol. 60 no. 8 2197-2201
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