Gender Differences in Serum Homocysteine Levels and Associated Variables

Overview

Background.
Homocysteine (Hcy) is an important independent risk factor for vascular diseases. It s level isdetermined by genetic polymorphism of several enzymes in association with nutritional factors. Higher Hcy levelswere found in men than in women, however the clinical significance of this phenomenon remains to be elucidated.The aim of this study was to analyze the gender differences in Hcy levels in relation to associated factors and toassess in which range of Hcy these differences are mainly expressed.Methods and Results. The series comprised of 257 males and 239 females, mean age 52.9 and 52.3 years, resp.,selected from the population study Pils II. All subjects were examined by a standard protocol, to assess clinical,anthropometrical and laboratory variables. Hcy and methionine levels were estimated by ion exchange chromatog-raphy, other laboratories using standard kits. The methods were validated by a reference laboratory. Statisticalanalyses were done by Wilcoxon’s unpaired test and multiple linear regression.We found in males significantly higher Hcy levels (13.1 vs. 11.5 mmol/l, p < 0.0001) than in females. This differencepersisted only in the range of normal Hcy levels (11.1, 10.2 mmol/l, p < 0.0001), i.e. up to 15 mmol/l (1st - 4th quintileof the Hcy distribution) and not in the top quintile, considered as mild hyperhomocysteinaemia. We found in males,with normal Hcy levels, significantly higher serum methionine (23.8 vs. 22.4 mmol/l, p < 0.0001), creatinine (91.5vs 80.9 mmol/l, p < 0.0001) and a lower methionine/creatinine ratio (0.25 vs. 0.27, p < 0.01). Plasma folates and B12vitamin in males were also lower than in females, however these differences were only of a borderline statisticalsignificance. On the other hand, in subjects with MHHcy (5th quintile) no gender differences were observed, exceptin creatinine.Conclusions. Higher Hcy levels in males cannot be explained by differences in folate and B12 levels only. Weconsidered also other factors, namely higher demethylation of methionine associated with higher creatinineproduction in males, which may be influenced by sex hormons.

Key words:
homocysteine, gender differences, methionine, folic acid, B12, creatinine.