Novel obesity risk loci do not determine distribution of body fat depots: a whole-body MRI/MRS study.

Obesity (Silver Spring)

Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls-University Tübingen, Tübingen, Germany.

Published: June 2010

A recent meta-analysis of genome-wide association studies has identified six new risk-loci for common obesity. We studied whether these risk loci influence the distribution of body fat depots. We genotyped 1,469 nondiabetic subjects for the single-nucleotide polymorphisms (SNPs) TMEM18 rs6548238, KCTD15 rs11084753, GNPDA2 rs10938397, SH2B1 rs7498665, MTCH2 rs10838738, and NEGR1 rs2815752. We assessed BMI, waist circumference, total body fat, and lean body mass (bioimpedance). All subjects underwent an oral glucose tolerance test (OGTT) for estimation of insulin sensitivity. In 332 subjects, we measured total adipose tissue (TAT), visceral adipose tissue (VAT), nonvisceral adipose tissue (NVAT), liver fat content, and intramyocellular lipids (IMCLs) using whole-body magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). In the dominant inheritance model, the risk alleles of TMEM18 rs6548238 and MTCH2 rs10838738 were nominally associated with higher BMI (P = 0.04, both). The risk allele of TMEM18 rs6548238 was additionally associated with higher waist circumference and total body fat (P 0.009, dominant inheritance model). Therefore, our results suggest that these new obesity SNPs, despite their influence on BMI, are neither associated with a metabolically unfavorable nor with a favorable body composition.

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http://dx.doi.org/10.1038/oby.2009.413DOI Listing

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