Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus.
OBJECTIVE
To analyze the relationship between the peroxisome proliferator-activated receptor-gamma (PPARgamma2) Pro12Ala variant and type-2 diabetes mellitus and its correlation with some cytokine determinants of insulin resistance such as tumor necrosis factor (TNF)-alpha and leptin.


METHODS
The PPARgamma2 Pro12Ala genetic polymorphism was studied in 167 type-2 diabetic patients and 63 healthy controls. Serum leptin and plasma-soluble TNF-R2 were measured.


RESULTS
Women carriers of the Pro12Ala mutation exhibited higher leptin levels than women non-carriers (median 31.4 vs. 17.5 ng/ml; p < 0.005). sTNF-R2 levels did not show differences between the two genotypes. Analysis by the multiple linear regression model of leptin-body mass index controlled by the PPARgamma2 genotype showed that leptin levels were determined by the Pro12Ala mutation in type-2 diabetic women but not in men.


CONCLUSIONS
PPARgamma2 seems to be implicated in leptin homeostasis in type-2 diabetic women.
Simón
I
I
Medicine and Surgery Department, University Hospital Joan XXIII, Tarragona, Institut d'Estudis Avançats, Universitat Rovira i Virgilli, Tarragona, Spain. ism@comt.es
Vendrell
J
J
Gutiérrez
C
C
Fernández-Real
J M
JM
Vendrell
I
I
Gallart
Ll
L
Fontova
R
R
Richart
C
C
D000368:Aged; D000409:Alanine; D000483:Alleles; D015703:Antigens, CD / Q000097:blood; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D020738:Leptin / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000097:blood; D011392:Proline; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics*; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II; D012727:Sex Characteristics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
D015703:Antigens, CD; D016207:Cytokines; C515448:LEPR protein, human; D020738:Leptin; D018160:Receptors, Cytoplasmic and Nuclear; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014157:Transcription Factors; D011392:Proline; D000409:Alanine