Factors explaining the difference of total homocysteine between men and women in the European investigation into cancer and nutrition Potsdam study

Interestingly, plasma total homocysteine (tHcy) concentration is consistent ly higher in men than in women. This observation deserves further investiga tions because elevated tHcy concentrations have been shown to be independen tly associated with coronary, peripheral, and cerebral vascular diseases. I t was the aim of the present study to define major determinants of plasma t Hcy in a healthy middle-aged German population under particular considerati on of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, a ged 40 to 65 years. Exclusion criteria were elevated creatinine levels in b lood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine. testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR). a key enz yme of folate and homocysteine metabolism, was determined by polymerase cha in reaction (PCR) with restriction enzyme analysis. In this population, pla sma tHcy ranged from 5 to 46 mu mol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, a nd 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No co rrelation was seen with vitamin B6. From the gender-related variables, tHcy correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was main ly explained by differences in fat-free mass, but also by estradiol concent rations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general popul ation has a variety of determinants ranging from nutrition, internal metabo lic parameters to gender-related variables. Copyright (C) 2001 by W.B. Saun ders Company.