Novel locus FER is associated with serum HMW adiponectin levels

Lu Qi, Claudia Menzaghi, Lucia Salvemini, Concetta De Bonis, Vincenzo Trischitta, Frank B. Hu

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 x 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.

Original languageEnglish
Pages (from-to)2197-2201
Number of pages5
JournalDiabetes
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 2011

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Adiponectin
Molecular Weight
Serum
Genome-Wide Association Study
Single Nucleotide Polymorphism
HDL Cholesterol
Type 2 Diabetes Mellitus
Fasting
Protein Isoforms
Homeostasis
Research Design
Nurses
Genome
Glucose
Health
Genes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Novel locus FER is associated with serum HMW adiponectin levels. / Qi, Lu; Menzaghi, Claudia; Salvemini, Lucia; De Bonis, Concetta; Trischitta, Vincenzo; Hu, Frank B.

In: Diabetes, Vol. 60, No. 8, 08.2011, p. 2197-2201.

Research output: Contribution to journalArticle

Qi, Lu ; Menzaghi, Claudia ; Salvemini, Lucia ; De Bonis, Concetta ; Trischitta, Vincenzo ; Hu, Frank B. / Novel locus FER is associated with serum HMW adiponectin levels. In: Diabetes. 2011 ; Vol. 60, No. 8. pp. 2197-2201.
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N2 - 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 x 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.

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