The peroxisome proliferator-activated receptor delta +294T/C polymorphism in relation to lipoprotein metabolism in patients with diabetes mellitus type 2 and in non-diabetic controls.
OBJECTIVE
Peroxisome proliferator-activated receptor delta (PPARdelta) is an ubiquitously expressed transcription factor that has been implicated in the regulation of genes related to cholesterol metabolism. Conflicting results exist regarding the association of the recently described +294T/C polymorphism in the 5'-untranslated region (5'-UTR) in exon 4 of the PPARdelta gene and plasma lipoprotein concentrations. Purpose of the present study was to examine for the first time in a German population and for the first time also in women the presence of a potential association between the aforementioned polymorphism and lipoprotein concentrations in patients with diabetes mellitus type 2 (DM-2) and in non-diabetic controls. Furthermore, a possible gene-gene interaction between the PPARdelta +294T/C polymorphism and the PPARalpha L162V polymorphism was examined.


METHODS
We determined by PCR the polymorphism in a total of 402 patients with DM-2 (230 men and 172 women) and in 436 healthy controls (248 men and 188 women) from the LIANCO study (lipid analytic cologne).


RESULTS
The genotype distribution was not different between DM-2 and controls (+294TT 65.6% versus 66.7%, +294TC 30.5% versus 29.4%, +294CC 3.9 versus 4.0%, respectively). There was no difference in the low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) or triglyceride (TG) concentrations between carriers and non-carriers of the rare C allele in the DM-2 population. In specific, the heterozygotes for the C allele had LDL-C concentrations of 157+/-80 mg/dl, HDL-C of 54+/-17 mg/dl and TG of 273+/-507 mg/dl, while the C allele homozygotes had concentrations of LDL-C 149+/-44 mg/dl, HDL-C of 59+/-21 mg/dl and TG of 197+/-110 mg/dl. The LDL-C, HDL-C and TG concentrations of TT homozygotes were 156+/-49 mg/dl, 56+/-18 mg/dl and TG 225+/-242 mg/dl, respectively. The same lack of association was present in the non-diabetic controls, both in men and in women. There was no association between the genotypes and body mass index. Furthermore, no gene-gene interaction between the PPARdelta +294TC and the PPARalpha L162V polymorphism was observed regarding lipoprotein concentrations and atherosclerotic disease.


CONCLUSIONS
The data suggest that the PPARdelta +294T/C polymorphism has no influence on plasma lipoprotein concentrations, body mass index or atherosclerotic disease either in healthy subjects or in patients with DM-2, both in males and females.
Gouni-Berthold
Ioanna
I
Department of Internal Medicine II, University of Cologne and Center of Molecular Medicine Cologne (CMMC), Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany. i.berthold@uni-bonn.de
Giannakidou
Eleni
E
Faust
Michael
M
Berthold
Heiner K
HK
Krone
Wilhelm
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004247:DNA / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047494:PPAR delta / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D047494:PPAR delta; D014280:Triglycerides; D004247:DNA