The MTHFR 677TT and 677CT/1298AC genotypes in Cypriot patients may be predisposing to hypertensive nephrosclerosis and chronic renal failure.
OBJECTIVE
The homozygous 677TT mutation of the MTHFR gene has been linked to deep vein thrombosis and to arterial atherosclerotic events of the coronary, carotid and peripheral arteries. Its putative association with renal arteriosclerosis and chronic renal failure (CRF) in the presence of hypertensive nephrosclerosis is yet to be investigated.


METHODS
Two hundred and twenty-one Greek-Cypriot patients with CRF from one single renal unit in Cyprus were divided into 6 diagnostic categories: 49 due to chronic glomerulonephritis (22.2%), 43 due to diabetes mellitus (19.4%), 26 due to autosomal dominant polycystic kidney disease (11.8%), 30 due to essential hypertension leading to nephrosclerosis (13.6%), including 4 patients with primary malignant hypertension, 32 with other rarer causes of CRF (14.5%) and 41 of uncertain etiology (18.5%). These 221 CRF patients had their MTHFR C677T and A1298C genotypes analyzed by the polymerase chain reaction and agarose gel electrophoresis after restriction enzyme digestion. The frequency of the homozygous states 677TT and 1298CC and the double heterozygous 677CT/1298AC were compared to those of 210 unrelated normal local controls.


RESULTS
A statistically significant increase in the frequency of the 677TT genotype compared to controls was only found in the hypertensive nephrosclerosis CRF sub-group of patients. The prevalence rate of the 677TT genotype was 46.7% (controls 17.6%, P=0.0007). Combined together the homozygous 677TT and the double heterozygous 677CT/1298AC genotypes were found in 86.7% of the hypertensive nephrosclerotic CRF patients, compared to 46.6% in normal controls (P=0.0001).


CONCLUSIONS
The findings support the hypothesis that Caucasian patients with essential hypertension, homozygous for 677TT or doubly heterozygous for 677CT/1298AC genotypes, are predisposed to develop hypertensive nephrosclerosis and CRF.
Koupepidou
P
P
Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
Deltas
C
C
Christofides
T C
TC
Athanasiou
Y
Y
Zouvani
I
I
Pierides
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003535:Cyprus; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006115:Greece / Q000208:ethnology; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D009400:Nephrosclerosis / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016036:Seroepidemiologic Studies; D044465:White People / Q000235:genetics
D017931:DNA Primers; D042965:Methylenetetrahydrofolate Reductase (NADPH2)