Methylenetetrahydrofolate reductase gene polymorphisms in essential hypertension relation: with the development of hypertensive end-stage renal disease.
BACKGROUND
The pathogenesis of hypertensive nephropathy is multifactoral and in addition to BP, other factors contribute to the development of this renal pathology and its progression to end-stage renal disease. These include genetic predisposition and increased pleasure level of homocysteine-intermediate protein catabolism product known to induce kidney injury. The 677C --> T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated homocysteine level in the general population, and therefore it has been hypothesized to be a risk factor for the development of renal failure in the course of essential hypertension.


METHODS
In this case-control, cross-sectional study the frequency of the MTHFR 677C --> T and the 1298A --> C polymorphism was compared between patients with hypertension-related chronic renal failure (n = 90), patients with essential hypertension without kidney injury (n = 90), and healthy individuals (n = 90) who were matched for age and gender. In addition, the influence of these polymorphisms on homocysteine concentration in individuals with essential hypertension was examined.


RESULTS
The frequency of the MTHFR 677 TT genotype did not differ between groups (4.5%, 12.3%, and 11.1%, respectively). Patients with hypertension and the 677TT genotype showed significantly higher homocysteine levels as compared to individuals having CC and CT. In the multivariate correlation analysis the MTHFR 677TT genotype (P < .01; beta = 0.27), age (P < .001; beta = 0.33), and body mass index (P < .01; beta = 0.3) were independent predictors for total homocysteine level.


CONCLUSIONS
Plasma homocysteine levels in individuals with essential hypertension is affected by the MTHFR 677C --> T polymorphism. However, we did not prove the hypothesis that MTHFR 677C --> T influences the risk of development of renal failure in the course of hypertension.
Tylicki
Leszek
L
Department of Nephrology, Transplantology and Internal Medicine. Medical University of Gdansk, Gdansk, Poland. leszek.tylicki@amg.gda.pl
Födinger
Manuela
M
Puttinger
Heidemarie
H
Rutkowski
Przemyslaw
P
Strozecki
Pawel
P
Tyszko
Sylwia
S
Rutkowski
Boleslaw
B
Hörl
Walter H
WH
D000483:Alleles; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)