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


METHODS
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.


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


METHODS
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. International Journal of Obesity (2000) 24, 206-210
Li
W D
WD
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Joo
E J
EJ
Furlong
E B
EB
Galvin
M
M
Abel
K
K
Bell
C J
CJ
Price
R A
RA
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009767:Obesity, Morbid / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin / Q000235:genetics*; D044465:White People / Q000235:genetics*
D017931:DNA Primers; D044104:Receptor, Melanocortin, Type 3; D018043:Receptors, Corticotropin