Impact of REV-ERB alpha gene polymorphisms on obesity phenotypes in adult and adolescent samples
Background: REV-ERBα has been shown to regulate adipogenesis and lipid metabolism as well as to link the circadian timing system to whole body metabolic homeostasis. We thus tested whether polymorphisms in REV-ERBα could be associated with metabolic phenotypes in human population samples. Methods: W...
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Veröffentlicht in: | International Journal of Obesity 2013-05, Vol.37 (5), p.666-672 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Background:
REV-ERBα has been shown to regulate adipogenesis and lipid metabolism as well as to link the circadian timing system to whole body metabolic homeostasis. We thus tested whether polymorphisms in
REV-ERBα
could be associated with metabolic phenotypes in human population samples.
Methods:
We analyzed the associations between 5
REV-ERBα
polymorphisms and anthropometric (body weight, body mass index (BMI), waist and hip circumferences), biochemical (plasma lipid, glucose and insulin levels) and clinical (systolic and diastolic blood pressure) variables in three population-based studies (MONICA Lille
n
=1155 adults, MONA LISA Lille
n
=1170 adults and HELENA
n
=1155 adolescents). We assessed
in vitro
, the potential influence of one
REV-ERBα
polymorphism in transient transfection assays using two different cell lines.
Results:
We observed significant and consistent associations between the T minor allele of the
REV-ERBα
rs2071427 polymorphism (located in intron 1) and higher BMI (mean allele effect=+0.33 kg m
−2
) in the MONICA Lille (
P
=0.02), MONA LISA (
P
=0.02) and HELENA (
P
=0.03) studies. The odds ratios for obesity associated with this allele were 1.67 (1.00–2.79) (
P
=0.05) in MONICA Lille, 1.29 (1.01–1.65) (
P
=0.04) in MONA LISA Lille and the odds ratio for overweight was 1.48 (1.08–2.03) (
P
=0.01) in HELENA. In transfection experiments in human hepatocyte-derived cell lines, the
REV-ERBα
intron 1 directed the transcription of a luciferase reporter gene independently of the rs2071427 polymorphism.
Conclusion:
Our results suggest that the
REV-ERBα
rs2071427 polymorphism modulates body fat mass in both adult and young people. |
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ISSN: | 0307-0565 1476-5497 0307-0565 |
DOI: | 10.1038/ijo.2012.117 |