An uncoupling protein 3 gene polymorphism associated with a lower risk of developing Type II diabetes and with atherogenic lipid profile in a French cohort.
OBJECTIVE
The UCP2-UCP3 gene region has been previously associated with obesity and diabetes. In a large representative cohort of Northern France (MONICA project), we studied the effect of a recently reported C/T polymorphism located in the 5' sequences of the UCP3 gene on anthropometric measurements and lipid profile. We also examined the association of this polymorphism with obesity and Type II (non-insulin-dependent) diabetes mellitus.


METHODS
The -55 C/T polymorphism of the UCP3 gene has been genotyped in 1155 subjects from the MONICA project. Association studies were done with diabetes, obesity and related phenotypes. Results were ascertained in a second cohort of well-characterized Type II diabetic and control subjects.


RESULTS
The variant T allele was associated with a decreased risk of developing Type II diabetes. Frequencies of the T allele were 13.3% compared with 22%, p = 0.04, in the diabetic and control groups, respectively. This observation was confirmed in the second cohort of French Type II diabetic (n = 171) and control (n = 124) subjects: 17.8% compared with 25%, p = 0.03. Moreover, subjects bearing the TT genotype had higher plasma total cholesterol and LDL-cholesterol concentrations (p = 0.0006 and p = 0.001, respectively) than subjects bearing wild or heterozygous genotypes.


CONCLUSIONS
The UCP3 -55 C/T polymorphism was associated with a higher atherogenic profile and modified the risk for the development of Type II diabetes.
Meirhaeghe
A
A
Department of Epidemiology and Public Health, INSERM U.508, Pasteur Institute of Lille, Central Hospital and University of Lille, France.
Amouyel
P
P
Helbecque
N
N
Cottel
D
D
Otabe
S
S
Froguel
P
P
Vasseur
F
F
D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D001824:Body Constitution; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D007473:Ion Channels; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009765:Obesity / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000071247:Uncoupling Protein 3
D001786:Blood Glucose; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D007328:Insulin; D007473:Ion Channels; D008055:Lipids; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3