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RARRES2, encoding the novel adipokine chemerin, is a genetic determinant of disproportionate regional body fat distribution: comparative mag
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| 09.05.2009, 14:12 |
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Abstract
Visceral fat mass is a strong and independent predictor of obesity-related disorders. To date, little is known about the genetic determinants
of regional body fat distribution in humans. As candidates of regional fat distribution, we investigated the fat mass – and obesity-associated
gene, the peroxisome proliferator –activated receptor–δ gene, and the retinoic acid receptor responder 2 (RARRES2) gene. We studied
whether genetic variation within these genes contributes to the development of disproportionate visceral obesity and obesity-related traits,
such as insulin resistance and β-cell dysfunction. We genotyped 337 subjects with an increased risk for type 2 diabetes mellitus for tagging
single nucleotide polymorphisms (SNPs) in the 3 genes and performed association analyses with anthropometric data and parameters of
insulin sensitivity and β-cell function. All subjects underwent an oral glucose tolerance test; a subset was additionally characterized by a
hyperinsulinemic-euglycemic clamp. Body fat distribution was assessed by nuclear magnetic resonance imaging. The fat mass – and obesityassociated
gene SNP rs8050136 was nominally associated with body mass index ( P = .0130), but not with body fat distribution, after
appropriate adjustment. Magnetic resonance imaging –quantified visceral fat mass was significantly associated with RARRES2 SNP
rs17173608 and nominally associated with RARRES2 SNP rs10278590 in nonobese subjects (P = .0002 and P = .0423, respectively), with
carriers of the minor alleles displaying lower visceral adipose tissue mass. Besides, the minor allele of SNP rs17173608 was nominally
associated with a lower waist-to-hip ratio ( P = .0295). In obese subjects, these associations were not detected. No associations were found
between the peroxisome proliferator –activated receptor–δ gene and measures of whole-body adiposity and of body fat distribution. All SNPs
were associated neither with insulin sensitivity nor with insulin secretion. Common genetic variation within RARRES2 is associated with
increased visceral fat mass in nonobese subjects. In generalized obesity, this genetic effect may be masked by the close association between
whole-body obesity and visceral fat mass.
© 2009 Elsevier Inc. All rights reserved.
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| Категория: Статьи | Добавил: nbylova
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