Association of sets of alleles of genes encoding beta3-adrenoreceptor, uncoupling protein 1 and lipoprotein lipase with increased risk of metabolic complications in obesity.
OBJECTIVE
To investigate the relationship between the polymorphisms of the beta3-AR (Trp64Arg), UCP1 (A-->G) and LPL (HindIII and PvuII) loci and the metabolic complications associated with obesity in a Turkish population.


METHODS
271 unrelated individuals of Turkish origin including obese (body mass index, BMI>30 kg¿m2) and lean (BMI< or =25 kg¿m2) subjects.


METHODS
Anthropometric (weight, height and blood pressure) and metabolic measurements (plasma levels of glucose, cholesterol and triglycerides), and determination of beta3-AR, UCP1 and LPL genotypes by polymerase chain reaction followed by enzymatic digestion.


RESULTS
The distributions of genotypes for each candidate gene (beta3-AR, UCP1 and LPL) were similar between the obese and the lean subjects. The Arg64 allele of the beta3-AR gene was absent from massively obese men. GG carriers of the A-->G variant of the UCP1 gene showed BMI-associated increases of cholesterol levels which were more marked than both AA (P=0.027) and AG (P=0.039) carriers. Obese P+ carriers of the LPL PvuII variant had significantly higher levels of glucose than non-carriers (P=0.011), whereas obese P+P+ carriers did not have significantly different levels of triglycerides than non-carriers (P=0.087). Moreover, carriers of both alleles (G&P+) had higher levels of glucose than non-carriers (P=0.048), but did not have significantly different levels of triglycerides than non-carriers (P=0.125). However, the BMI-associated increase of triglycerides of P+&G carriers was significantly more marked than that of P+ carriers (P=0.0085).


CONCLUSIONS
Our data support the idea that alleles of specific genes (UCP1, LPL and beta3-AR) might play a role in the development of certain metabolic complications of obesity and might have additive effects when combined with each other (as in the case of UCP1 and LPL). International Journal of Obesity (2000)24, 93-100
Proenza
A M
AM
Institut Cochin de Génétique Moléculaire, Laboratoire d'ImmunoPharmacologie Moléculaire, CNRS UPR 0415 and Université de Paris VII 22, rue Méchain, 75014 Paris, France.
Poissonnet
C M
CM
Ozata
M
M
Ozen
S
S
Guran
S
S
Palou
A
A
Strosberg
A D
AD
D000328:Adult; D000483:Alleles; D000886:Anthropometry; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007473:Ion Channels; D008071:Lipoprotein Lipase / Q000097:blood / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D024101:Mitochondrial Proteins; D009765:Obesity / Q000097:blood / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011943:Receptors, Adrenergic, beta / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D014421:Turkey; D000071256:Uncoupling Protein 1
D001786:Blood Glucose; D002352:Carrier Proteins; D017931:DNA Primers; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011943:Receptors, Adrenergic, beta; D014280:Triglycerides; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D002784:Cholesterol; D008071:Lipoprotein Lipase