An association between the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and inflammation markers related to cardiovascular disease.
BACKGROUND
Prospective studies have identified many markers of systemic inflammation that are powerful predictors of future cardiovascular events. The methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a common polymorphism that induces hyperhomocysteinaemia, has been proposed as a genetic risk factor for cardiovascular disease. In this work, we evaluated the relationship between the levels of inflammation markers and MTHFR genotype among cardiovascular disease free subjects of the ATTICA study.


METHODS
During 2001-2002, we randomly enrolled for genetic evaluation 574 subjects from Attica region, Greece. In this work, we investigated demographic, lifestyle, clinical, biochemical and genetic information from 322 men (46+/-13 years) and 252 women (45+/-14 years). Among other characteristics, we measured various inflammatory markers levels in relation to C677T MTHFR genotype distribution.


RESULTS
The MTHFR genotypes distribution was: homozygous normal (CC) genotype, 41%; heterozygous (CT), 48%; and homozygous mutant (TT) genotype, 11%. C-reactive protein (CRA), fibrinogen, white blood cell (WBC) counts and amyloid-a levels were higher in TT compared to CC and CT genotypes (p<0.01), in both genders, even after controlling for various potential confounders.


CONCLUSIONS
The observed association between markers of systemic inflammation with MTHFR genotype may state a hypothesis for a common pathobiological mechanism between inflammation process and MTHFR, which is a key enzyme in homocysteine (Hcy) metabolism.
Dedoussis
George V Z
GV
Department of Dietetics and Nutrition, Harokopio University, 46 Paleon Polemiston St. Glyfada, Attica 166 74, Athens, Greece.
Panagiotakos
Demosthenes B
DB
Pitsavos
Christos
C
Chrysohoou
Christina
C
Skoumas
John
J
Choumerianou
Despoina
D
Stefanadis
Christodoulos
C
D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000235:genetics / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005838:Genotype; D006710:Homocysteine / Q000032:analysis; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D000685:Serum Amyloid A Protein / Q000032:analysis
D000685:Serum Amyloid A Protein; D006710:Homocysteine; D005340:Fibrinogen; D002097:C-Reactive Protein; D042965:Methylenetetrahydrofolate Reductase (NADPH2)