rs567754
mixedMag 3.2This is a intron variant variant in the BHMT gene.
Key Literature Trait Associations
Betaine-Homocysteine Methylation
The BHMT-02 variant (rs567754) is an intronic polymorphism in betaine-homocysteine S-methyltransferase, which provides an alternative pathway to remethylate homocysteine to methionine using betaine as the methyl donor. Published evidence for the independent clinical significance of this intronic variant is very limited.
Selenium levels
The T allele of rs567754 at the BHMT locus is associated with lower toenail selenium concentrations at genome-wide significance (p < 1×10⁻¹⁶) in European cohorts, with a separate study of blood selenium confirming association at the same 5q14 region (combined n = 9,639). A smaller GWAS (n = 428) of selenium response to supplementation did not achieve genome-wide significance at this locus, though nearby BHMT-region SNPs showed nominal associations. The BHMT enzyme's role in homocysteine–selenium pathway crosstalk may explain why genetic variation here influences selenium homeostasis beyond dietary intake.
Triglycerides in small VLDL
In the UK Biobank NMR metabolomics GWAS (n ≈ 450,000), rs567754-T was associated with lower triglycerides in small VLDL particles (beta = −0.01 mmol/L, p = 4×10⁻¹¹). This effect likely reflects downstream perturbation of lipid metabolism through altered methionine cycle flux rather than a direct lipid gene effect. The biological magnitude of this triglyceride shift is small, though the statistical evidence is robust given the large sample size.
Triglyceride to phosphoglyceride ratio
rs567754-T is also associated with a lower circulating triglyceride-to-phosphoglyceride ratio (beta = −0.01, p = 1×10⁻¹⁰) in the same large UK Biobank NMR metabolomics GWAS of ~450,000 individuals. This association likely reflects the same underlying metabolic perturbation as the small VLDL triglyceride finding, with the BHMT locus influencing lipid particle composition through one-carbon pathway effects. The absolute effect size is small and unlikely to be independently clinically actionable.
▶GWAS Catalog Trait Associations (3)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (3)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶Research that mentions this SNP (3)
▶MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian populationAssociationN=1,712Sibele Nascimento de Aquino et al.(2014)· Birth Defects Research Part A: Clinical and Molecular Teratology
Case-control study of 501 young stroke patients and 1,211 controls examining 58 polymorphisms in 17 genes involved in methionine metabolism. Multiple logistic regression identified four independent risk factors for early-onset ischaemic stroke: rs10037045 BHMT (OR 1.38, p=0.033), rs682985 BHMT2 (OR 1.46, p=0.017), rs1051319 CBS (OR 3.75, p<0.0001), and rs202680 FOLH1 (OR 3.00, p<0.0001). Haplotype analyses identified significant associations with BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes and stroke risk.
▶Folate pathway and nonsyndromic cleft lip and palateAssociationN=445Susan H. Blanton et al.(2011)· Birth Defects Research Part A: Clinical and Molecular Teratology
This family-based association study examined 14 folate pathway genes using 89 SNPs in 445 NSCLP families (317 non-Hispanic White, 128 Hispanic) to identify genetic variants contributing to nonsyndromic cleft lip and palate. Evidence for association was found with SNPs in NOS3 and TYMS in the non-Hispanic White group (rs2373929/NOS3, rs502396/TYMS, and others), and with MTR, BHMT2, MTHFS, and SLC19A1 in the Hispanic group (rs1422086/BHMT2, rs2115540/MTHFS significant after Bonferroni correction). Multiple gene-gene interactions were detected, with CBS and MTHFD1 showing the most extensive interactions. Significant interactions were also found between several SNPs and maternal smoking and one SNP (rs651646/FOLR2) with offspring sex.
▶Oral facial clefts and gene polymorphisms in metabolism of folate/one‐carbon and vitamin A: a pathway‐wide association studyAssociationN=425Abee L. Boyles et al.(2009)· Genetic Epidemiology
A pathway-wide association study in 425 case-parent triads examined 109 SNPs in 29 folate/one-carbon metabolism genes and 68 SNPs in 16 vitamin A metabolism genes for associations with cleft lip/palate (CL/P) and cleft palate only (CPO). Despite strong epidemiologic evidence that folic acid and vitamin A reduce cleft risk, no convincing genetic associations were found; the strongest association was FOLH1 with CPO (p=0.0008), but findings were fewer than expected by chance and inconsistent with protective effects of vitamin supplementation, suggesting vitamin metabolism gene polymorphisms do not play an etiologic role in oral facial clefts.
Gene information from NCBI Gene. Variant classifications from ClinVar.
Community Wiki
No community notes yet for this variant. Sign in to start one.
Comments
Sign in to join the discussion.
Loading comments…