Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele.
The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5,035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women.


BACKGROUND
The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk.


METHODS
We studied 5,035 individuals from the Rotterdam Study, >or=55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4,646 individuals (2,692 women).


RESULTS
In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677-T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 microM, p = 0. 01; trend, p = 0.02).


CONCLUSIONS
In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women.
Yazdanpanah
Nahid
N
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Uitterlinden
André G
AG
Zillikens
M Carola
MC
Jhamai
Mila
M
Rivadeneira
Fernando
F
Hofman
Albert
A
de Jonge
Robert
R
Lindemans
Jan
J
Pols
Huibert Ap
HA
van Meurs
Joyce B
JB
D000368:Aged; D000483:Alleles; D015519:Bone Density; D015331:Cohort Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D005494:Folic Acid Deficiency / Q000150:complications*; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology*; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D015994:Incidence; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications; D017698:Postmenopause; D012256:Riboflavin / Q000008:administration & dosage; D012257:Riboflavin Deficiency / Q000150:complications*; D012307:Risk Factors
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D012256:Riboflavin