Influence of 699C -> T and 1080C -> T polymorphisms of the cystathionine beta-synthase gene on plasma homocysteine levels

The association of moderately elevated total homocysteine (tHcy) levels wit h coronary artery disease is increasingly being recognized. However, the ro le of genetic influence on plasma tHcy levels is not completely understood. We studied 1055 individuals with respect to the effect of two silent polym orphisms, the 699C --> T and the 1080C --> T, of the cystathionine beta -sy nthase (CBS) gene on plasma tHcy levels. Individuals who were heterozygous or homozygous for the T-699 allele had lower post-methionine load (PML) tHc y levels when compared to individuals with the C/C genotype. This associati on was statistically significant (p = 0.005) for the T/T genotype compared to the C/C genotype and became even more significant (p = 0.000002) when in dividuals carrying the 68-bp insertion (844ins68) and the T-1080 allele wer e excluded from the analysis. With regard to the 1080C --> T polymorphism, the T-1080 allele was associated with significantly lower PML tHcy levels o nly when individuals carrying the 844ins68 and T699 allele were excluded fr om the study (p = 0.01 for 1080T/T genotype compared to 1080C/C genotype). We speculate that the 699C --> T and 1080C --> T polymorphisms may be in li nkage disequilibrium with regulatory elements that upregulate CBS gene tran scription.