Association of C677T polymorphism in MTHFR gene, high homocysteine and low HDL cholesterol plasma values in heterozygous familial hypercholesterolemia.

Aim: 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).

Methods: 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.

Results: 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.

Conclusion: 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.