The G Allele of Transcobalamin 2 c.776C→G Is Associated with an Unfavorable Lipoprotein Profile

Abstract

Background/Aim: 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). Conclusion: 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.

Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults

“…Additional findings from that study implicated SNP in the genes for transcobalamin II (rs1801198) and MTHFR (rs1801133) were associated with blood lipid profiles. The G allele of rs1801198 was correlated with higher levels of LDL in plasma, lower HDL, higher triglyceride levels, and higher total cholesterol levels [3]. However, in our study, neither rs1801198 (transcobalamin II) nor rs1801133 ( MTHFR ) were statistically significantly associated with levels of HDL in plasma.…”

“…In that study, SLC19A1 (SNP rs1051266) was not found to have a statistically significant association with blood lipid profiles analysed (fasting lipoprotein, total cholesterol, LDL, HDL, and triglyceride levels) [3]. Additional findings from that study implicated SNP in the genes for transcobalamin II (rs1801198) and MTHFR (rs1801133) were associated with blood lipid profiles.…”

“…High levels of Hcy and changes in plasma lipids are independent risk factors for development of CVD, and there may be a connection between Hcy metabolism and lipid metabolism [3]. Low levels of dietary folate, an important cofactor in the metabolism of Hcy, led to increased levels of serum and liver cholesterol in wild-type mice [4].…”