(Stroke. 2000;31:983-f.)
© 2000 American Heart Association, Inc.
Letters to the Editor |
The A677V MTHFR Allele Is Not Associated With Carotid Atherosclerosis in Octogenarians
Department of Clinical and Experimental Medicine, Section of Internal Medicine II, University of Ferrara, Ferrara, Italy
Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
To the Editor:
We read with interest the article by Bova et al,1
published in the October 1999 issue of Stroke, on the
association of the MTHFR A677V gene allele with carotid
atherosclerosis. We have just finished a study aimed to
characterize very old people with "vascular successful aging"
(VSA), which we define according to the following criteria: (1) age
75 years; (2) negative history for cardiovascular
disease; (3) absence of clinical symptoms and
ultrasonographic/Doppler signs (duplex sonography) of
extracoronary (epiaortic, abdominal aortic, iliac, and femoral)
atherosclerosis, ie, lack of any focal protrusion
1.5 mm; and (4) absence of clinical symptoms and ECG signs of
coronary artery disease. These subjects were compared with a
control group selected by the following criteria: (1) age 75 years
and (2) presence of carotid atherosclerosis, ie, a
plaque inducing a 30% to 50% stenosis. They may have a
positive history for cardiovascular disease, provided
that no acute episode occurred in the 3 months before inclusion in the
study. A total of 57 subjects, 29 with VSA and 28 with carotid
atherosclerosis (AG), were enrolled. The mean age in
both groups was >80 years (80.9 and 81.8, respectively). We found
several differences between the VSA subjects and controls in plasma and
LDL antioxidant levels as well as in LDL oxidation level. Among the
possible genetic markers of vascular successful aging, we also
determined the A677V MTHFR gene polymorphism by the method of
Frosst et al,2 but we did not find any association with
the vascular status. The frequency of the A677V allele was 52% in
the VSA group and 39% in the AG group (
2=NS), while the
frequency of homozygosity was 36% in VSA and 10% in the AG group
(2=NS). Genotype frequencies conformed to the
Hardy-Weinberg equilibrium. In the study of Bova et al, the subjects
were significantly younger than in our study and the control group
suffered from mild carotid atherosclerosis. Because
atherosclerosis is a progressive disease, subjects with
a mild stenosis in adult age, as the control group
presented in the study, might develop greater stenosis
in late life and therefore might not represent an ideal control
for comparison. Moreover, only 19% of the subjects with severe carotid
atherosclerosis were homozygous, a condition that has
been clearly associated with increased homocysteine
levels.2
Our results suggest that this polymorphism is not associated with the presence, or with the absence, of moderate to severe carotid atherosclerosis in very advanced age. However, it is possible that the A677V gene polymorphism is associated with atherosclerosis in a younger population as well as in different ethnic groups.
Because the relationship between A677V gene polymorphism and carotid atherosclerosis is still controversial,3 4 more research must be done in this field before any conclusion can be drawn.
References
1.
Bova I, Chapman J, Sylantiev C, Korczyn AD,
Bornstein NM. The A677V
methylenetetrahydrofolate reductase
gene polymorphysm and carotid atherosclerosis.
Stroke.. 1999;30:2180–2182.
2. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers CJH, den Heiljer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R. A candidate genetic risk factor for vascular disease: a common mutation in methylentetrahydrofolate reductase. Nat Genet.. 1995;10:111–113. Letter.[Medline] [Order article via Infotrieve]
3. Kostulas K, Huang WX, Lannfelt L, Hagenfeldt L, Egertsen G. A methylentetrahydrofolate reductase gene polymorphysm in ischaemic stroke and in carotid artery stenosis. Eur J Clin Invest.. 1998;28:285–289.[Medline] [Order article via Infotrieve]
4.
Spence JD, Malinow MR, Barnett PA, Marian AJ, Freeman D,
Hegele RA. Plasma homocysteine concentration, but not MTHFR
genotype, is associated with variation in carotid plaque area.
Stroke.. 1999;30:969–973.
Response
Stroke Unit, Department of Neurology, Tel Aviv Sourasky Medical Center
Department of Neurology and, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
We thank Zuliani and colleagues for describing their
observations on carotid stenosis and the MTHFR 677c-t
allele. As these authors note, their patient population was
significantly older than the patients in our study and were chosen by
somewhat different criteria. In this population the MTHFR 677c-t
allele was less common in patients with moderate carotid
stenosis than in age-matched patients with no significant
cardiovascular disease. Although it is difficult to
compare our study with the results of Zuliani et al, the differences
between elderly and younger patients seem to be analogous with the
well-established association of the APOE 
4 allele and
Alzheimer’s disease. In the case of APOE, the 4 allele
is associated with earlier age of onset of disease; due to earlier
mortality in Alzheimer’s disease, in the population aged >80
years it is no longer more common in Alzheimer patients than in
controls.R1 R2
References
1. Scacchi R, De Bernardini L, Mantuano E, Donini LM, Vilardo T, Corbo RM. Apolipoprotein E (APOE) allele frequencies in late-onset sporadic Alzheimer’s disease (AD), mixed dementia and vascular dementia: lack of association of epsilon 4 allele with AD in Italian octogenarian patients. Neurosci Lett.. 1995;201:231–234.[Medline] [Order article via Infotrieve]
2.
Corder EH, Saunders AM, Strittmatter WJ, Schmechel
DE, Gaskell PCJ, Rimmler JB, Locke PA, Conneally PM, Schmader KE, Tanzi
RE, al e. Apolipoprotein E, survival in Alzheimer’s disease
patients, and the competing risks of death and Alzheimer’s
disease. Neurology.. 1995;45:1323–1328.
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