Genotype frequencies and linkage disequilibrium in the CEPH human diversity panel for variants in folate pathway genes MTHFR, MTHFD, MTRR, RFC1, and GCP2.
BACKGROUND
Genetic variation in enzymes involved in vitamin metabolism is a candidate for analysis in studies of how nutritional covariates may impact a disease state. The role of folate pathway genes in birth defects and cardiovascular disease in humans has been widely studied. Since incidence rates for these disorders vary by geographic origins, it is useful to know which variants are the best candidates for studies based on genotype and allele frequency, as well as linkage disequilibrium (LD) in founder populations.


METHODS
Six polymorphisms in five folate metabolism-related genes (MTHFR, MTHFD, MTRR, GCP2, and RFC1) were genotyped on a collection of 1064 DNA samples from populations around the world, which were made available by the Centre d'Etude du Polymorphisme Humain (CEPH) consortium for analysis.


RESULTS
In this study we report the genotype frequencies for variants in the MTHFR, MTHFD, MTRR, GCP2, and RFC1 genes, and the LD for two variants (C677T and A1298C) in MTHFR.


CONCLUSIONS
The rare allele frequency for each of the five genes studied varied widely. LD is strongest in Pakistani and Brazilian populations (D' = 1.0) and weakest in Mexican populations (D' = 0.45). These findings will allow the selection of variants that will provide the most power in studies of folate pathway genes involving different ancestral populations, and contribute to our knowledge of the population distribution of selected nutritional gene variants.
Shi
Min
M
Biology Department, University of Iowa, Iowa City, Iowa 52242, USA.
Caprau
Diana
D
Romitti
Paul
P
Christensen
Kaare
K
Murray
Jeffrey C
JC
D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction
D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; C120043:SLC19A2 protein, human; C112305:TUBGCP2 protein, human; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)