Association of C677T polymorphism in MTHFR gene, high homocysteine and low HDL cholesterol plasma values in heterozygous familial hypercholesterolemia.
to investigate the association of C677T polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene, homocysteine plasma values (Hcy), and plasma HDL cholesterol in heterozy-gous familial hypercholesterolemia (hFH). One hundred and twenty-five hFH subjects were studied. Plasma lipid, lipoprotein, vitamin B12, folic acid and Hcy values were determined. C677T polymorphism in the MTHFR gene was detected by SSCP-PCR. Genetic diagnosis of FH was determined by a three-step protocol using SSCP-PCR, Southern blot, long PCR and automatic sequencing. We found significant differences in plasma HDL-C (CC 1.39+/-0.34, CT 1.33+/-0.39 and TT 1.14+/-0.26 mmol/L, p=0.028) between the C677T MTHFR genotypes, that were also found when gender age, and BMI were included as covariables. In addition, Hcy values were significantly different between C/T MTHFR genotypes (CC 11.75+/-2.9, CT 12.69+/-2.88, TT 15.34+/-2.1 micromol/L). The distribution of gender, smoking habit and LDLR gene mutations was similar among the three groups.A significant correlation was found between Hcy plasma values and plasma HDL-C (-0.370, p= 0.003), but no correlations were found with age, BMI or other lipid and apo B plasma values. In hFH subjects, the genotype TT and higher plasma Hcy levels were associated with lower HDL-C plasma values in FH subjects. More studies are needed to confirm our results and also to elucidate the exact mechanism of interaction between plasma homocysteine and lipid metabolism.DOI: