[Leptin level and the PPARgamma2 Pro12Ala and Pro115Gln polymorphisms in women with functional hyperandrogenism. Preliminary report].
Hyperandrogenism is a multifactoral chronic disease, characterised by an androgen excess, often connected with obesity, hirsutism, polycystic ovaries, hyperinsulinemia, insulin resistance and hyperleptynemia. Peroxisome proliferator activated receptors (PPARgamma) are one of the factors influencing insulin sensitivity. As a transcriptional factor it plays a crucial role in the regulation of genes involved in insulin action. The aim of this study was to evaluate the frequency of PPARgamma Pro12Ala and Pro115Gln polymorphisms in hyperandrogenic women. The additional aim was to investigate differences in leptin levels in healthy and FOH (functional ovarian hyperandrogenism) women (non-obese and obese).


METHODS
we investigated 90 women: 72 healthy women (37 nonobese and 35 obese)--control group, and 18 women with FOH (9 nonobese and 9 obese)--FOH group. We performed anthropological examination: BMI, WHR and total-body densytomery, biochemical and hormonal estimations in the whole group. PPARgamma polymorphism was studied using PCR and RFLP.


RESULTS
in the control group Pro12Pro ("wild" type) was observed in 45 women (26 obese and 19 nonobese) - 62.5% of the group. Heterozygosity Pro12Ala was observed in 15 women (20.8%): 4 obese and 11 with BMI < 30 kg/m2, homozygosity Ala12Ala was seen in 12 women (16.6%): 5 obese i 7 nonobese. In FOH group "wild" type was discovered in 9 women (4 obese and 5 nonobese) - 50% of FOH group, heterozygosity Pro12Ala was seen in 5 women (27.7%): 2 obese and 3 with BMI < 30 kg/m2, homozygosityAla12Ala was observed in 4 women (22.2%): 3 obese and in 1 non-obese. Ala allel frequency in control group was 28%. (37% in non-obese and 20% in obese). In FOH group Ala allel frequency was 36% (nonobese - 28%, obese - 44%). In the studied group we did not find Pro115Gln polymorphism. Leptin level in control group was 19.92 +/- 14.3 ng/ml, and in FOH group - 23.41 +/- 19.47 ng/ml. Depending on BMI leptin level in non-obese healthy group was 7.45 +/- 3.76 ng/ml, in non-obese FOH women - 18.33 +/- 16.54 ng/ml, p < 0.005. In obese controls leptin level was 43.6 +/- 17.28 ng/ml, and in obese FOH women - 45.72 +/- 14.89 ng/ml.


CONCLUSIONS
Leptin level in non-obese FOH women is significantly higher than in lean healthy controls. This difference was not observed in obese women. However the Pro12Ala polymorphism is quite common; it does not seem to be directly related to the obesity connected with hyperandrogenism. Higher frequency of Ala allele In FOH women compared to healthy controls (36% vs 28%) may at least partially explain the beneficial effect of tiazolidinediones in the treatment of hyperandrogenism.
Klinika Endokrynologii, Diabetologii i Leczenia Izotopami, Akademii Medycznej we Wrocławiu. bobi@kom-net.pl
Bozena
B
Bidzińska-Speichert
Marek
M
Demissie
Urszula
U
Tworowska
Ryszard
R
Slezak
Tadeusz
T
Dobosz
Grazyna
G
Bednarek-Tupikowska
Andrzej
A
Milewicz
D000328:Adult; D000483:Alleles; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D017588:Hyperandrogenism / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D047495:PPAR gamma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*
D020738:Leptin; D047495:PPAR gamma