Folate intake and the MTHFR C677T genotype influence choline status in young Mexican American women.

Numerous studies have reported a relationship between folate status, the methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant and disease risk. Although folate and choline metabolism are inter-related, only limited data are available on the relationship between choline and folate status in humans. This study sought to examine the influences of folate intake and the MTHFR 677C-->T variant on choline status. Mexican-American women (n=43; 14 CC, 12 CT and 17 TT) consumed 135 microg/day as dietary folate equivalents (DFE) for 7 weeks followed by randomization to 400 or 800 microg DFE/day for 7 weeks. Throughout the study, total choline intake remained unchanged at approximately 350 mg/day. Plasma concentrations of betaine, choline, glycerophosphocholine, phosphatidylcholine and sphingomyelin were measured via LC-MS/MS for Weeks 0, 7 and 14. Phosphatidylcholine and sphingomyelin declined (P=.001, P=.009, respectively) in response to folate restriction and increased (P=.08, P=.029, respectively) in response to folate treatment. The increase in phosphatidylcholine occurred in response to 800 (P=.03) not 400 (P=.85) microg DFE/day (week x folate interaction, P=.017). The response of phosphatidylcholine to folate intake appeared to be influenced by MTHFR C677T genotype. The decline in phosphatidylcholine during folate restriction occurred primarily in women with the CC or CT genotype and not in the TT genotype (week x genotype interaction, P=.089). Moreover, when examined independent of folate status, phosphatidylcholine was higher (P<.05) in the TT genotype relative to the CT genotype. These data suggest that folate intake and the MTHFR C677T genotype influence choline status in humans.

Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype.

Since the establishment of the 1998 folate recommended dietary allowance (RDA), the methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant has emerged as a strong modifier of folate status. This controlled feeding study investigated the adequacy of the RDA, 400 microg/d as dietary folate equivalents (DFE), for Mexican American men with the MTHFR 677CC or TT genotype. Because of the interdependency between folate and choline, the influence of choline intake on folate status was also assessed. Mexican American men (n = 60; 18-55 y) with the MTHFR 677CC (n = 31) or TT (n = 29) genotype consumed 438 microg DFE/d and total choline intakes of 300, 550 (choline adequate intake), 1100, or 2200 mg/d for 12 wk. Folate status response was assessed via serum folate (SF), RBC folate, plasma total homocysteine (tHcy), and urinary folate. SF decreased (P < 0.001) 66% to 7.9 +/- 0.7 nmol/L (means +/- SEM) in men with the 677TT genotype and 62% to 11.3 +/- 0.9 nmol/L in the 677CC genotype. Plasma tHcy increased (P < 0.0001) 170% to 31 +/- 3 micromol/L in men with the 677TT genotype and 18% to 11.6 +/- 0.3 micromol/L in the 677CC genotype. At the end of the study, 34% (677TT) and 16% (677CC) had SF concentrations <6.8 nmol/L and 79% (677TT) and 7% (677CC) had tHcy concentrations >14 micromol/L. Choline intake did not influence the response of the measured variables. These data showed that the folate RDA is not adequate for men of Mexican descent, particularly for those with the MTHFR 677TT genotype, and demonstrated a lack of influence of choline intake on the folate status variables measured in this study.

The MTHFR 677TT genotype and folate intake interact to lower global leukocyte DNA methylation in young Mexican American women.

DNA methylation is an epigenetic feature that is associated with X chromosome inactivation, genomic imprinting, transcriptional silencing of genes and genomic stability. Folate provides a labile source of methyl groups which may be used for cellular methylation reactions including DNA methylation. The methylenetetrahydrofolate reductase (MTHFR) 677C-->T variant is an important determinant of folate nutriture and may influence DNA methylation. This study sought to assess the influence of the MTHFR C677T genotype on global leukocyte DNA methylation in young (18-45y) Mexican American women (n=43; 14 CC, 12 CT and 17 TT). Subjects consumed a folate restricted diet (135 mug DFE/d) for 7 wk followed by folate treatment with 400 or 800 mug DFE/d for 7 wk. Global leukocyte DNA methylation was assessed via the cytosine extension assay at week 0, week 7 (after folate restriction) and week 14 (after folate treatment). No main effects of MTHFR C677T genotype or folate intake were detected at any time point during the study. However, at the end of folate treatment (wk 14), DNA methylation was lower (P<0.05) in women with the MTHFR 677TT genotype relative to the CT or CC genotype. Because it is unlikely that folate treatment would result in methyl group loss, we suggest that there was a delay in DNA methylation response to folate intake. Overall, these data suggest that the MTHFR 677TT genotype and folate interact to lower global leukocyte DNA methylation patterns in young Mexican American women.

Health related quality of life among adults reporting arthritis: analysis of data from the Behavioral Risk Factor Surveillance System, US, 1996-99.

OBJECTIVE: To characterize health related quality of life (HRQOL) among people with and without self-reported arthritis in the general population by selected demographic and behavior characteristics. METHODS: We analyzed data from a cross sectional random-digit telephone survey [the Behavioral Risk Factor Surveillance System (BRFSS)] of civilian noninstitutionalized adults aged 18 years or older from 15 states and Puerto Rico, all of which used an optional arthritis survey module for one or more years from 1996 through 1999. We compared HRQOL among people with arthritis, defined as chronic joint symptoms (CJS) or doctor-diagnosed arthritis, those within one of 3 arthritis subgroups (i.e., only doctor-diagnosed arthritis, only CJS, and both doctor-diagnosed arthritis and CJS), and those without arthritis. RESULTS: On an age-adjusted basis, respondents with arthritis had significantly worse HRQOL than respondents without arthritis. Members of all 3 arthritis subgroups had significantly worse HRQOL than those without arthritis. Those with both CJS and doctor-diagnosed arthritis had consistently worse HRQOL than those with only CJS, who in turn had worse HRQOL than those with only doctor-diagnosed arthritis. In some of the demographic and behavioral subgroups, HRQOL differences between those with and without arthritis greatly exceeded the differences for the overall study. CONCLUSION: Because many adults report arthritis and because arthritis substantially worsens their HRQOL, HRQOL measures like those in the BRFSS may be useful in monitoring the burden of arthritis and in tracking the success of population interventions for arthritis.