Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wall.
BACKGROUND
The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the internal elastic lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries.


METHODS
The autopsy study included 123 subjects (90 males and 33 females) aged 18-93. For the light microscopy, a 0.5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis.


RESULTS
The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2.02 +/- 2.25 vs. 2.53 +/- 1.89, P < 0.04 and 0.56 +/- 1.09 vs. 1.82 +/- 2.66, P < 0.02, respectively). The trend was similar for the coeliac and the right renal arteries.


CONCLUSIONS
Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL.
Hämelahti
P
P
Department of Clinical Chemistry, Tampere University Hospital Tampere, Finland.
Järvinen
O
O
Sisto
T
T
Wirta
V
V
Ilveskoski
E
E
Koivula
T
T
Lehtimäki
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology; D002445:Celiac Artery / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D017537:Mesenteric Artery, Inferior / Q000473:pathology; D017538:Mesenteric Artery, Superior / Q000473:pathology; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D012077:Renal Artery / Q000473:pathology; D018709:Statistics, Nonparametric; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)