Are fasting plasma homocyst(e)ine levels heritable? A study of normotensive twins

Background: Plasma homocyst(e)ine levels (pHo) can be a risk marker for car diovascular diseases. Different factors affect pHo, but it remains unclear whether pHo are genetically determined and whether they are related to othe r risk markers, such as the angiotensin I converting enzyme (ACE) and the p lasminogen activator inhibitor type-1 (PAI-1), Methods: We measured fasting pHo, plasma levels of ACE (pACE), and PAI-1 an tigen (PAI-1:ag) in 60 pairs of healthy monozygotic (MZ) and dizygotic (DZ) normotensive twins. Twin zygosity was determined with polymerase chain rea ction analysis of informative minisatellite markers. pHo data were first an alyzed with TWINAN90 to obtain estimates of genetic variance and heritabili ty and then examined jointly in a path analysis. Results: Thirty-one twins were MZ and 29 DZ, The mean pHo were 10.48+/-4.07 mu mol/L (95% confidence interval, 9.73-11.24 mu mol/L). Two pairs had to be excluded from further analysis because of overt hyperhomocyst(e)inemia r esulting from concomitant drug treatment, Highly statistically significant intraclass correlation coefficients were observed both in MZ (r=0.421; P=0. 008) and in DZ (r=0.488; P=0.004). Because all tests of genetic variance an d heritability were not significant, the hypothesis of genetic variance and heritability of pHo was rejected. The preferred model of a likelihood-base d analysis included an additive genetic influence (A), a common environment al influence (C), and an individually unique environmental influence (E), a ccounting for 8%, 39%, and 53%, of pHo variance, respectively, No relations hip between pHo and pACE or PAI-1:ag was detected, Conclusions: These data do not support the contention that normal-to-border line elevated pHo of healthy subjects are heritable and under major genetic influence. They suggest that E and C are far more important than A in dete rmining pHo variance. Furthermore, they provide no evidence of a relationsh ip of pHo with pACE and PAI-1:ag.