rs2066470

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This is a synonymous variant in the MTHFR gene — it does not change the protein's amino acid sequence.

Key Literature Trait Associations

Congenital heart disease

Two candidate-gene studies in Chinese populations found associations between maternal rs2066470 genotype and congenital heart disease (CHD) in offspring. Zhong et al. (2022, n=1,209) reported an adjusted OR of 5.09 (95% CI: 1.99–13.03) for the AA versus GG genotype in mothers of CHD cases, with significant interaction between MTHFR genotype and periconceptional folic acid supplementation status. Sun et al. (2021, n=1,221) identified a two-locus interaction model involving rs2066470 and rs1801131 as a predictor of CHD risk. Both studies are limited to Han Chinese populations and await independent replication.

Zhong T et al. “Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.” Frontiers in Pediatrics (2022)

Allele A

OR 5.09

p —

N 1,209

Preliminary work

East Asian

Sun M et al. “Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring.” Bmc Cardiovascular Disorders (2021)

Allele A

OR —

p —

N 1,221

Preliminary work

East Asian

Lean body mass

Liu et al. (2008) examined MTHFR haplotype variants in 1,873 individuals from 405 Caucasian nuclear families and found that rs2066470 was significantly associated with lean body mass (p=0.0006), accounting for approximately 3.67% of lean body mass variation in the sample. Notably, no significant associations were detected between rs2066470 and fat body mass, suggesting a tissue-specific effect restricted to muscle-related compartments. This finding has not been independently replicated in large-scale GWAS.

Xiaogang Liu et al. “The MTHFR gene polymorphism is associated with lean body mass but not fat body mass” Human Genetics (2008)

Allele A

OR —

p 6.0e-4

N 1,873

Preliminary work

European

Folate Metabolism

The MTHFR P39P variant (rs2066470) is a synonymous SNP in the 5' region of the MTHFR gene. The A allele has been associated with modestly increased risk of neural tube defects in some populations, possibly through effects on mRNA stability. Its functional impact is much smaller than the well-established C677T (rs1801133) variant.

Chiamaka N. Aneji et al. “Deep sequencing study of the <i>MTHFR</i> gene to identify variants associated with myelomeningocele” Birth Defects Research Part A: Clinical and Molecular Teratology (2012)

Allele A

OR —

p —

N 96

Candidate gene study

multi-ancestry

Pulikkunnel ST et al. “Neural tube defects: pathogenesis and folate metabolism.” The Journal of the Association of Physicians of India (2005)

Allele A

OR 1.20

p 4.0e-2

Candidate gene study

Chang MH et al. “Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.” American Journal of Epidemiology (2009)

Allele A

OR —

p —

N 7,159

Preliminary work

multi-ancestry

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ClinVar annotation

Benign★☆☆☆

8 submitters2 publications

Homocystinuria due to methylene tetrahydrofolate reductase deficiency; not specified

View on ClinVar →

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Research that mentions this SNP (2)

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Deep sequencing study of the MTHFR gene to identify variants associated with myelomeningocele

AssociationN=96Chiamaka N. Aneji et al.(2012)· Birth Defects Research Part A: Clinical and Molecular Teratology

This deep sequencing study of the MTHFR gene identified variants associated with myelomeningocele (a neural tube defect) in 96 affected subjects (49 Caucasian, 47 Mexican American). The authors discovered one novel intronic splice site variant (c.171+3G>T) and found seven SNPs with significant allele frequency differences compared to ethnically matched reference populations (p ≤ 0.05, Fisher's exact test), including five SNPs (rs13306561, rs2274976, rs2066462, rs12121543, rs1476413) not previously associated with neural tube defects.

Traits studied:MyelomeningoceleNeural tube defectsSpina bifida

PubMed DOI Metascience Observatory

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The MTHFR gene polymorphism is associated with lean body mass but not fat body mass

AssociationN=1,873Xiaogang Liu et al.(2008)· Human Genetics

This candidate gene association study examined five SNPs in the MTHFR gene in 405 Caucasian nuclear families (1,873 individuals) and found significant associations between MTHFR polymorphisms and lean body mass (LBM). rs2066470 (P = 0.0006), rs4846048 (P = 0.0007), and rs3737964 (P = 0.004) were associated with LBM, with rs2066470 explaining 3.67% of LBM variation. BMI associations with rs4846048 (P = 0.009) were mediated through LBM. No associations were found with fat body mass.

rs2066470

Key Literature Trait Associations

Congenital heart disease

Lean body mass

Folate Metabolism

ClinVar annotation

Research that mentions this SNP (2)

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