Abstract
Total blood levels of homocysteine (tHcy) have been shown to depend on both environmental
and genetic factors, and to be associated with the risk of developing atherosclerosis
with its complications of coronary heart disease (CHD) and stroke. In this study,
408 men and 346 women from two towns, Dewsbury and Maidstone were examined for tHcy
levels and genotyped for the C677T and the A1298C polymorphisms in the methylenetetrahydrofolate
reductase (MTHFR) gene. Blood tHcy was significantly higher in men from the CHD high
risk town of Dewsbury (12.7 μmol/l) than in the low CHD risk town of Maidstone (11.5
μmol/l) P<0.001, but not in women (10.7 vs. 10.5 μmol/l), with women in both towns, thus, showing
significantly lower tHcy than men. There was no difference between towns in folate
or vitamin B12 levels but the conventional inverse relationship with tHcy was seen. Smoking men
and women from both towns had significantly higher tHcy and lower folate levels than
non-smoking individuals (P<0.001). The frequency of the 677T allele in Dewsbury was 0.35 (95% CI; 0.32–0.39)
compared with 0.29 (95% CI; 0.26–0.32) in Maidstone (P<0.01). Similar frequency difference of borderline statistical significance was seen
both for men (P=0.054) and women (P=0.048) in both the towns, suggesting a true regional frequency difference. The effect
of the 677T on tHcy was highly significant in the group as a whole with the most profound
effect seen in men (12.0 μmol/l for CC vs. 14.1 μmol/l for TT, P<0.001). By contrast, there was no significant effect of the A1298C polymorphism on
tHcy, folate or vitamin B12 levels, with no evidence for an interaction with the C677T genotype. The regional
differences in tHcy levels were still present after the adjustment for folate and
vitamin B12 levels, smoking and the effect of the C677T polymorphism. This suggests that there
may be other unidentified factors, either environmental or genetic, affecting tHcy
levels, and thus potentially having an impact on the risk of developing hyperhomocysteinaemia
and CHD. These observations may have a bearing on regional differences in tHcy levels
and the variation in CHD risk between regions in the UK.
Keywords
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Article info
Publication history
Accepted:
April 28,
2000
Received in revised form:
April 17,
2000
Received:
October 26,
1999
Identification
Copyright
© 2001 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
