rs1801181

badMag 2.5

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

Key Literature Trait Associations

Transsulfuration Pathway

The CBS A360A variant (rs1801181) is a synonymous polymorphism in cystathionine beta-synthase. The A allele has been associated with altered CBS enzyme activity in the transsulfuration pathway. Some studies suggest it may influence homocysteine to cystathionine conversion, but evidence is less robust than for the C699T variant (rs234706).

Allele A
OR
p 1.8e-2
N 244
Candidate gene study
European
Allele A
OR
p 2.0e-2
Candidate gene study
Lievers KJ et al. Cystathionine beta-synthase polymorphisms and hyperhomocysteinaemia: an association study. European Journal of Human Genetics : Ejhg (2003)
Allele A
OR
p
N 571
Preliminary work
European

Coronary artery disease

The CBS 1080C>T polymorphism (rs1801181) has been examined in relation to coronary artery disease (CAD) risk in small candidate-gene studies. Kruger et al. (2000, n=244) found that C allele homozygotes (i.e., T/T at rs1801181) were underrepresented among CAD patients compared to controls (29.6% vs 44.2%, p=0.018), suggesting the T allele may modestly increase CAD risk. A Spanish case-control study (Urreizti et al., 2007, n=253) reported that a CBS haplotype including the c.1080C allele was associated with elevated CAD risk (OR=2.16, 95% CI 1.29–3.63), though the haplotype effect makes it difficult to isolate rs1801181 alone. Given the small sample sizes and absence of large-scale replication, this association is considered preliminary.

Allele A
OR
p 1.8e-2
N 244
Candidate gene study
European
Allele A
OR 2.16
p
N 253
Candidate gene study
European

Delayed cerebral ischemia

A prospective observational study (Grobelny et al., 2011) of 87 patients with aneurysmal subarachnoid hemorrhage found that the CBS 1080 TT genotype (homozygous for the T/A allele at rs1801181) was significantly more prevalent among patients who developed delayed cerebral ischemia (DCI) compared to CC and CT genotypes (p=0.042). The TT genotype was classified as a decrease-in-function allele, suggesting that reduced CBS activity and impaired transsulfuration pathway flux may predispose to vasospasm-related cerebral ischemia following intracranial hemorrhage. This finding is based on a small single-center study and requires replication in larger cohorts.

Allele A
OR
p 4.2e-2
N 87
Candidate gene study
European

Non-Hodgkin lymphoma

A population-based case-control study (Li et al., 2013) of 518 NHL cases and 597 controls in Connecticut women found a borderline significantly increased risk of non-Hodgkin lymphoma associated with rs1801181 (CBS Ex13+41C>T). The association was dependent on dietary nutrient intakes, consistent with the gene-nutrient interaction framework for one-carbon metabolism polymorphisms and lymphoma risk. No specific odds ratio was reported for rs1801181 in the abstract. This finding is unreplicated and should be considered exploratory.

Allele A
OR
p
N 1,115
Preliminary work
European

ClinVar annotation

Benign★★★
18 submitters3 publications

Classic homocystinuria; Familial thoracic aortic aneurysm and aortic dissection (TAAD); HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED; not specified

View on ClinVar →

Research that mentions this SNP (4)

Folate pathway and nonsyndromic cleft lip and palate
AssociationN=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.

Traits studied:NSCLPNonsyndromic cleft lip and palate
Genetic variants in one‐carbon metabolism‐related genes contribute to NSCLC prognosis in a Chinese population
AssociationN=564Guangfu Jin et al.(2010)· Cancer

This association study screened 57 SNPs from 11 one-carbon metabolism genes in 564 NSCLC patients to identify genetic variants affecting lung cancer prognosis. Key findings included favorable prognostic associations for MTR rs3768160 A>G (HR=0.78, 95% CI 0.62-0.98), MTRR rs2966952 G>A (HR=0.84, 95% CI 0.71-0.99), and DHFR rs1650697 G>A (HR=0.83, 95% CI 0.70-0.99), with unfavorable prognosis for MTHFD1 rs1950902 G>A (HR=1.18, 95% CI 0.99-1.40). Combined analysis of these four SNPs demonstrated a locus-dosage effect on NSCLC survival (P trend = 6.9×10⁻⁵) and identified combined genotypes as an independent prognostic factor.

Traits studied:Lung cancer survivalNon-small cell lung cancer (NSCLC) prognosis
Variability in Ethanol Biodisposition in Whites Is Modulated by Polymorphisms in the Adh1b and Adh1c Genes
ReviewCarmen Martínez et al.(2010)· Hepatology

A comprehensive review of nutrigenetics and nutrigenomics examining how genetic variants influence individual responses to nutrients and dietary interventions. The paper discusses associations between numerous SNPs (rs9939609 in FTO, rs2287019 in GIPR, rs7903146 in TCF7L2, rs5219 in KCNJ11, and many others) and metabolic traits including obesity, type 2 diabetes, and other chronic diseases, along with epigenetic mechanisms by which phytochemicals (curcumin, resveratrol, lycopene) modulate gene expression. The review synthesizes current evidence for precision nutrition approaches tailored to individual genetic profiles.

Traits studied:Bone density/osteoporosisCaffeine sensitivityCardiovascular diseaseCeliac diseaseCerebrovascular diseaseCoronary heart diseaseDetoxification capacityEating behaviorGlucose homeostasisHistamine intoleranceInflammatory diseasesInsulin resistanceLactose intoleranceLeptin resistanceMetabolic syndromeNickel intoleranceObesityOsteoarthritisOverweightType 2 diabetes
Folate metabolism genes, vegetable intake and renal cancer risk in central Europe
AssociationN=2,652Moore LE et al.(2008)· International Journal of Cancer

A case-control study of 1,097 renal cell carcinoma (RCC) cases and 1,555 controls in Central and Eastern Europe examined common genetic variation in 5 folate metabolism genes. Variants in MTHFR (A222V rs1801133) and TYMS (IVS2-405C rs502396) were significantly associated with RCC risk, with the MTHFR variant increasing risk (OR=1.44) particularly in groups with low vegetable intake, while TYMS variant reduced risk (OR=0.73). The associations demonstrated significant gene-nutrient interactions with vegetable consumption.

Traits studied:Renal cell carcinoma

Gene information from NCBI Gene. Variant classifications from ClinVar.

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