Titre du document / Document title

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

Auteur(s) / Author(s)

LI W.-D. ⁽¹⁾ ; JOO E.-J. ⁽¹⁾ ; FURLONG E. B. ⁽²⁾ ; GALVIN M. ⁽²⁾ ; ABEL K. ⁽²⁾ ; BELL C. J. ⁽²⁾ ; PRICE R. A. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, ETATS-UNIS
⁽²⁾ Axys Pharmaceuticals, La Jolla, CA, ETATS-UNIS

Résumé / 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, lle → 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.

Revue / Journal Title

International journal of obesity   ISSN 0307-0565   CODEN IJOBDP 

Source / Source

2000, vol. 24, n^o2, pp. 206-210 (31 ref.)

Langue / Language

Anglais

Editeur / Publisher

Nature Publishing, Basingstoke, ROYAUME-UNI  (1977) (Revue)

Mots-clés anglais / English Keywords

Obesity ; Genetic variant ; Hormonal receptor ; Genetic determinism ; Nucleotide sequence ; Single strand conformation polymorphism ; Pathogenesis ; Human ; Nutritional status ; Nutrition disorder ;

Mots-clés français / French Keywords

Obésité ; Variant génétique ; Récepteur hormonal ; Déterminisme génétique ; Séquence nucléotide ; Polymorphisme conformation simple brin ; Pathogénie ; Homme ; Etat nutritionnel ; Trouble nutrition ;

Mots-clés espagnols / Spanish Keywords

Obesidad ; Variante genética ; Receptor hormonal ; Determinismo genético ; Secuencia nucleótido ; Polimorfismo conformación cadena única ; Patogenia ; Hombre ; Estado nutricional ; Trastorno nutricíon ;

Localisation / Location

INIST-CNRS, Cote INIST : 18243, 35400008663701.0110