title: Association of C677T polymorphism in MTHFR gene, high homocysteine and low HDL cholesterol plasma values in heterozygous familial hypercholesterolemia.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hospital Clínico Universitario, Department of Medicine, University of Valencia, Spain.
authors.forename: Jose T
authors.initials: JT
authors.lastname: Real
authors.forename: Sergio
authors.initials: S
authors.lastname: Martinez-Hervas
authors.forename: Ana Barbara
authors.initials: AB
authors.lastname: Garcia-Garcia
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Chaves
authors.forename: Miguel
authors.initials: M
authors.lastname: Civera
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ascaso
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D011973:Receptors, LDL; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)