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Sequence variants in the melatonin-related receptor gene (GPR50) associate with circulating triglyceride and HDL levels

Authors :
Sumit Bhattacharyya
Jian'an Luan
Benjamin Challis
Julia Keogh
Carl Montague
John Brennand
John Morten
Sarah Lowenbeim
Suzanne Jenkins
I. Sadaf Farooqi
Nicholas J. Wareham
Stephen O'Rahilly
Source :
Journal of Lipid Research, Vol 47, Iss 4, Pp 761-766 (2006)
Publication Year :
2006
Publisher :
Elsevier, 2006.

Abstract

The gene encoding the melatonin-related receptor (GPR50) is highly expressed within hypothalamic nuclei concerned with the control of body weight and metabolism. We screened GPR50 for mutations in an obese cohort and identified an insertion of four amino acid residues (TTGH) at position 501, two common coding polymorphisms (T528A and V602I), and one noncoding polymorphism (C-16X2GPR50T). Single-nucleotide polymorphisms were then typed in 500 English Caucasian subjects, and associations were sought to intermediate obesity phenotypes. Although no association was seen with body mass index, carriers of two copies of the mutant allele at C-16X2GPR50T, Ins501Del, and A1582G had significantly higher fasting circulating triglyceride levels (P < 0.05). In a separate set of 585 subjects, the associations were replicated, with statistically significant effects of similar magnitude and direction. The association of C-16X2GPR50T with fasting triglycerides was highly significant (P < 0.001). In addition, a significant association between C-16X2GPR50T and circulating HDL levels was observed in the combined population, with C-16X2GPR50T carriers having significantly lower circulating HDL-cholesterol levels (1.39 mM) than wild-type subjects (1.47 mM) (P < 0.01). These findings suggest a previously unexpected role for this orphan receptor in the regulation of lipid metabolism that warrants further investigation.

Details

Language :
English
ISSN :
00222275
Volume :
47
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Journal of Lipid Research
Publication Type :
Academic Journal
Accession number :
edsdoj.3d0351a925ae41e893b1c277edaaa59f
Document Type :
article
Full Text :
https://doi.org/10.1194/jlr.M500338-JLR200