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Melanocortin 3 receptor (MC3R) gene variants in extremely obese women

International Journal of Obesity volume 24, pages 206–210 (2000)Cite this article

Abstract

OBJECTIVE: Following several reports of linkage of obesity related phenotypes to human chromosome 20q we sought to determine whether variations of the melanocortin 3 receptor (MC3R) gene are associated with obesity.

DESIGN: We screened the MC3R gene coding region and approximately 2 kb of 5′ and 3′ flanking sequences for DNA variants in unrelated extremely obese women and average weight controls using polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) analysis and DNA sequencing.

SUBJECTS: 124 unrelated extremely obese women (body mass index, (BMI)≥40 kg/m2) and 85 average weight controls (BMI<27 kg/m2).

MEASUREMENTS: Radiation hybrid (RH) mapping was performed to localize the MC3R gene. 5′ and 3′ flanking sequences of MC3R gene were cloned. PCR-SSCP and DNA sequencing were used to detect mutations in the MC3R gene coding region and flanking sequences.

RESULTS: RH mapping localized the MC3R gene to 20q13, between markers D20S100 and D20S149. 1083 bp 5′ and 653 bp 3′ flanking region of the MC3R gene were cloned. A missense mutation (+241, codon 81 ATT/GTT, Ile→Val) was found in the MC3R coding region. Four more variants were detected in the 5′ flanking sequence: −201(C→G), −239 (A→G), −762(A→T) and −769(T→C). Compared with controls, no significant allele frequency differences were found. Racial differences were found for the +241, −201, −239 and −762 polymorphisms.

CONCLUSIONS: Several sequence variants were found in the MC3R gene coding region and in 5′ flanking sequences. However, none of the variants were associated with obesity phenotypes. The linkage of extreme human obesity on 20q13 is likely caused by genes other than MC3R.

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Acknowledgements

This work was supported by the National Institutes of Health (NIH; R01DK44073 and R01DK48095), and Axys Pharmaceuticals and Glaxo Wellcome (RAP, PI). Collection of mental health controls was supported by P01MH43880 (Raquel E. Gur, PI). We acknowledge the cooperation of our subjects. We thank Guang Ming Yuan, Robin L. Kilker, Nicholas Guido, Andrew C. Krakowski, Balasahib Shinde, Sami Weisberg, Christa A. Mayr, Elizabeth Joe, Kruti Quazi, Karynn Henry, Paula Kown, Timothy Gasperoni, Richard Joseph, Duc Bach and sequencing technical assistance from Axys. Drs. Joseph H. Lee and Danielle R. Reed commented on earlier drafts.

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  1. E-J Joo

    Present address: Department of Psychiatry, Eulji Medical School, Daejon, Korea

Authors and Affiliations

  1. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

    W-D Li, E-J Joo & R Arlen Price

  2. Axys Pharmaceuticals, La Jolla, CA, USA

    EB Furlong, M Galvin, K Abel & CJ Bell

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  1. W-D Li
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Correspondence to R Arlen Price.

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Li, WD., Joo, EJ., Furlong, E. et al. Melanocortin 3 receptor (MC3R) gene variants in extremely obese women. Int J Obes 24, 206–210 (2000). https://doi.org/10.1038/sj.ijo.0801114

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