Peroxisome proliferator-activated receptor-gamma2 Pro12Ala and endothelial nitric oxide synthase-4a/b gene polymorphisms are not associated with hypertension in diabetes mellitus type 2.
OBJECTIVE
The Pro12Ala and the 4a/b polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARgamma) and the endothelial nitric oxide-synthase (eNOS) genes, respectively, have been associated with hypertension in some but not all studies. The purpose of this study was to investigate the association between these polymorphisms and hypertension in patients with diabetes mellitus type 2 (DM2).


METHODS
We determined, by polymerase chain reaction (PCR), the Pro12Ala PPARgamma2 and the eNOS 4a/b gene polymorphisms in a total of 395 patients with diabetes mellitus 2 (DM2) (225 men and 170 women) from the LIANCO (Lipid-Analytic-Cologne) study. Hypertension was defined as known or newly diagnosed hypertension according to current national guidelines. Associations were determined using chi-square statistics. The influence of genotype and other parameters on blood pressure was determined by analysis of variance (ANOVA) and multivariate analyses.


RESULTS
The genotype frequencies of the Pro12Ala polymorphism were 3% AlaAla, 23% ProAla and 74% ProPro and of the eNOS 4a/b polymorphism 3% a/a, 25% b/a and 72% b/b. There were 65% patients with, and 35% without hypertension. A total of 77% of the patients with hypertension were under pharmacological treatment. The mean systolic and diastolic blood pressure (SBP, DBP) was 148 +/- 22 and 84 +/- 11 mmHg in patients with, and 131 +/- 12 and 79 +/- 8 mmHg in patients without, hypertension. There was no difference in the occurrence of hypertension among ProAla and AlaAla subjects compared with ProPro subjects (P = 0.98). There was also no difference between a-allele carriers and non-carriers of the eNOS polymorphism (P = 0.42). There were no differences between men and women in the associations. Analysis of variance did neither identify an influence on systolic or diastolic blood pressure by the presence of the Ala or the a-allele of the respective genotypes nor a significant interaction of the two.


CONCLUSIONS
In DM2 the Pro12Ala and 4a/b gene polymorphisms of the PPARgamma2 and eNOS genes, respectively, are not associated with systolic or diastolic blood pressure, either in men or in women. Our results in a large cohort fail to confirm reports of recent studies suggesting an association of lower blood pressure in patients with DM2 and carriers of Pro12Ala polymorphism.
Gouni-Berthold
Ioanna
I
Department of Internal Medicine II, University of Cologne and Center of Molecular Medicine Cologne (CMMC), Cologne, Germany. i.berthold@uni-bonn.de
Giannakidou
Eleni
E
Müller-Wieland
Dirk
D
Faust
Michael
M
Kotzka
Jörg
J
Berthold
Heiner K
HK
Krone
Wilhelm
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000235:genetics; D000704:Analysis of Variance; D001794:Blood Pressure / Q000235:genetics; D016009:Chi-Square Distribution; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D012189:Retrospective Studies
D047495:PPAR gamma; D011392:Proline; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000409:Alanine