Becky L Tsang1, Owen J Devine1, Amy M Cordero1, Claire M Marchetta1, Joseph Mulinare1, Patricia Mersereau1, Jing Guo1, Yan Ping Qi1, Robert J Berry1, Jorge Rosenthal1, Krista S Crider1, Heather C Hamner2. 1. From the Division of Birth Defects and Developmental Disabilities, National Center for Birth Defects and Developmental Disabilities (NCBDDD), CDC, Atlanta, GA (AMC, RJB, JR, and KSC); the Division of Nutrition, Physical Activity, and Obesity, National Center on Chronic Disease Prevention and Health Promotion, CDC, Atlanta, GA (HCH); Acentia (contractor for CDC, NCBDDD), Falls Church, VA (JG); Carter Consulting Inc. (contractor for CDC, NCBDDD), Atlanta, GA (OJD, JM, and YPQ); the Oak Ridge Institute for Science and Education, Oak Ridge, TN (BLT, CMM, and YPQ); SciMetrika LLC (contractor for CDC, NCBDDD), Atlanta, GA (PM). 2. From the Division of Birth Defects and Developmental Disabilities, National Center for Birth Defects and Developmental Disabilities (NCBDDD), CDC, Atlanta, GA (AMC, RJB, JR, and KSC); the Division of Nutrition, Physical Activity, and Obesity, National Center on Chronic Disease Prevention and Health Promotion, CDC, Atlanta, GA (HCH); Acentia (contractor for CDC, NCBDDD), Falls Church, VA (JG); Carter Consulting Inc. (contractor for CDC, NCBDDD), Atlanta, GA (OJD, JM, and YPQ); the Oak Ridge Institute for Science and Education, Oak Ridge, TN (BLT, CMM, and YPQ); SciMetrika LLC (contractor for CDC, NCBDDD), Atlanta, GA (PM). hfc2@cdc.gov.
Abstract
BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations. OBJECTIVE: We assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women aged 12-49 y. DESIGN: We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes. RESULTS: Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only. CONCLUSIONS: Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects.
BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations. OBJECTIVE: We assessed the association between MTHFRC677T genotypes and blood folate concentrations among healthy women aged 12-49 y. DESIGN: We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFRC677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes. RESULTS: Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only. CONCLUSIONS: Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFRC677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects.