The G allele of transcobalamin 2 c.776C→G is associated with an unfavorable lipoprotein profile.
OBJECTIVE
Recent studies have suggested a relation of homocysteine with lipid metabolism. The aim of this study was to analyze a possible genetic basis for such a relation in 504 individuals including 135 consecutive Caucasian patients diagnosed with cerebrovascular disease as well as the patients' healthy spouses (n = 100) and offspring (n = 269).


METHODS
We analyzed the association of plasma levels of lipoprotein(a), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides with plasma homocysteine levels and with the following 7 variants of homocysteine metabolism: dihydrofolate reductase c.594 + 59del19bp, cystathionine β-synthase c.844_855ins68, methionine synthase c.2756A→G, methylenetetrahydrofolate reductase c.677C→T and c.1298A→C, reduced folate carrier 1 c.80G→A, and transcobalamin 2 (Tc2) c.776C→G.


RESULTS
Linear regression analysis showed an association of Tc2 c.776C→G with LDL (p = 0.010), HDL (p = 0.009), and TG (p = 0.007), with the G allele of Tc2 c.776C→G associated with an unfavorable blood lipid profile. Moreover, the G allele of Tc2 c.776C→G was associated with higher homocysteine plasma levels in the subgroup of patients (p = 0.013, 1-way ANOVA).


CONCLUSIONS
These data support the hypothesis that alterations in homocysteine metabolism and an unfavorable blood lipoprotein profile may have a common genetic basis. Such conditions may be relevant for studies investigating independent risk factors for vascular disease.
Department of Neurology, University of Zürich, Frauenklinikstrasse 26, Zürich, Switzerland.
Alexander
A
Semmler
Susan
S
Farmand
Susanna
S
Moskau
Birgit
B
Stoffel-Wagner
Michael
M
Linnebank
D000328:Adult; D000368:Aged; D000483:Alleles; D002561:Cerebrovascular Disorders / Q000503:physiopathology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein / Q000378:metabolism; D014155:Transcobalamins / Q000235:genetics* / Q000378:metabolism; D044465:White People
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D058978:Reduced Folate Carrier Protein; D014155:Transcobalamins; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)