ECE2009 Poster Presentations Obesity and Metabolism (70 abstracts)
Melanocortin-4-receptor gene variants: hotspot or identical by descent?
Jessica Grothe 1 , Harald Brumm 1 , André Scherag 4 , Susann Friedel 3 , Anke Hinney 3 , Johannes Hebebrand 3 , Thomas Illig 2 , Harald Grallert 2 , Susanna Wiegand 1 , Heiko Krude 1 , Sadaf Farooqi 5 , Annette Grüters 1 & Heike Biebermann 1
1Institute of Experimental Pediatric Endocrinology, Charité Campus Virchow-Klinikum, Berlin, Germany; 2Helmholtz Zentrum München, Institute of Epidemiology, German Research Center for Environmental Health, München, Germany; 3Department of Child and Adolescent Psychiatry, Rheinische Kliniken Essen, University of Duisburg-Essen, Essen, Germany; 4Institut für Medizinische Informatik, Biometrie und Epidemiologie Universitätsklinikum Essen, Essen, Germany; 5Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK.
The melanocortin-4-receptor (MC4R) plays an important role in body weight regulation. Mutations in the MC4R gene are the most common genetic cause for obesity. The most frequent Northern European mutation is Y35X, associated with D37V on the same allele. Furthermore, there are two variants with a relatively high frequency: V103I and S127L. In rare cases, we identified the variants V103I and S127L on the same allele. The occurrence of two variants on the same allele makes a founder effect possible but this has yet to be proven. Therefore, we analysed single nucleotide polymorphisms (SNPs) within a range of overall 240 kb up- and downstream of the MC4R gene. Our sample group consisted of a healthy control group and of trios of normal weight and obese patients of Caucasian origin. We analysed 25 mutation carriers of Y35X/D37V, three V103I/S127L carriers and their families and two Arab families each with two homozygous carriers of a pathogenic missense mutation, C271R.
Linkage disequilibrium (LD) analyses show that the investigated SNPs form three different LD-blocks. In a first attempt we focused on those SNPs forming an LD-block that comprises the coding region of the MC4R gene for haplotype analysis. Aside from 11 different haplotypes we found one main haplotype with a frequency of approximately 73% in the control trios. Via analysis of the mutation carriers we could show that the Y35X/D37V mutation is estimated to be always located on this common haplotype making a founder effect highly possible. The double mutation V103I/S127L is located on another haplotype as well as the C271R mutation which indicate identity by decent. In conclusion, we can show that the increased prevalence of certain MC4R mutations, Y35X/D37V and V103I/S127L in Caucasian and C271R in patients of Arab origin, can be attributed to a founder effect in these populations.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more