An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes.
OBJECTIVE
Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis.


METHODS
Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing.


RESULTS
In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p < 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76).


CONCLUSIONS
We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin.
Cassell
P G
PG
Medical Unit and Clinical Biochemistry, St. Bartholomew's and The Royal London School of Medicine and Dentistry, United Kingdom.
Neverova
M
M
Janmohamed
S
S
Uwakwe
N
N
Qureshi
A
A
McCarthy
M I
MI
Saker
P J
PJ
Albon
L
L
Kopelman
P
P
Noonan
K
K
Easlick
J
J
Ramachandran
A
A
Snehalatha
C
C
Pecqueur
C
C
Ricquier
D
D
Warden
C
C
Hitman
G A
GA
D000328:Adult; D000818:Animals; D015992:Body Mass Index; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000208:ethnology; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008875:Middle Aged; D024101:Mitochondrial Proteins; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D000071246:Uncoupling Protein 2; D006113:United Kingdom / Q000453:epidemiology; D014504:Urban Health
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2