Are Fasting Plasma Homocyst(e)ine Levels Heritable? A Study of Normotensive Twins

Abstract

Background

Plasma homocyst(e)ine levels (pHo) can be a risk marker for cardiovascular diseases. Different factors affect pHo, but it remains unclear whether pHo are genetically determined and whether they are related to other risk markers, such as the angiotensin I converting enzyme (ACE) and the plasminogen activator inhibitor type-1 (PAI-1).

Methods

We measured fasting pHo, plasma levels of ACE (pACE), and PAI-1 antigen (PAI-1:ag) in 60 pairs of healthy monozygotic (MZ) and dizygotic (DZ) normotensive twins. Twin zygosity was determined with polymerase chain reaction analysis of informative minisatellite markers. pHo data were first analyzed with TWINAN90 to obtain estimates of genetic variance and heritability 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 µmol/L (95% confidence interval, 9.73-11.24 µmol/L). Two pairs had to be excluded from further analysis because of overt hyperhomocyst(e)inemia resulting 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 and heritability were not significant, the hypothesis of genetic variance and heritability of pHo was rejected. The preferred model of a likelihood-based analysis included an additive genetic influence (A), a common environmental influence (C), and an individually unique environmental influence (E), accounting for 8%, 39%, and 53%, of pHo variance, respectively. No relationship between pHo and pACE or PAI-1:ag was detected.

Conclusions

These data do not support the contention that normal-to-borderline 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 determining pHo variance. Furthermore, they provide no evidence of a relationship of pHo with pACE and PAI-1:ag.