rs2287780

badMag 2.5

This is a variant in the MTRR gene that changes a arginine to an cysteine.

Key Literature Trait Associations

Colorectal cancer

Two candidate-gene studies in predominantly European cohorts have examined rs2287780 (MTRR Arg415Cys) in relation to colorectal neoplasia. Koushik et al. (2006) found that carriers of the Cys415 variant allele had an OR of 2.03 (95% CI 1.15–3.56) for colorectal cancer compared to homozygous wild-type in the Nurses' Health Study / Health Professionals Follow-up Study. Hazra et al. (2007) reported a suggestive association with advanced colorectal adenoma in women. Both studies are relatively small and lack genome-wide significance; large GWAS catalogs do not include this variant, so findings require confirmation in larger, independent populations.

Koushik A et al. “Nonsynonymous polymorphisms in genes in the one-carbon metabolism pathway and associations with colorectal cancer.” Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology (2006)

Allele T

OR 2.03

p —

N 1,225

Preliminary work

European

Hazra A et al. “Twenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and risk of colorectal adenoma in the Nurses' Health Study.” Carcinogenesis (2007)

Allele T

OR —

p —

N 1,113

Cohort

European

Hepatocellular carcinoma

A Chinese case-control study (Zhang et al., 2015) of 1,500 HCC patients and 1,500 controls found that MTRR rs2287780 was significantly associated with hepatocellular carcinoma risk in a Chinese population (p range 2.26×10⁻⁴–0.035 across six one-carbon pathway SNPs). The study was conducted in a hepatitis B virus (HBV)-endemic setting and participants were matched by age, sex, and HBV status. Specific OR and confidence interval for rs2287780 alone were not reported in the abstract. Evidence is limited to this single candidate-gene study in an East Asian population and has not been replicated or confirmed in GWAS.

Zhang H et al. “Genetic variations in the one-carbon metabolism pathway genes and susceptibility to hepatocellular carcinoma risk: a case-control study.” Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine (2015)

Allele T

OR —

p 2.3e-4

N 3,000

Preliminary work

East Asian

Methionine Synthase Reductase Activity

The MTRR R415T variant (rs2287780) is a rare missense polymorphism (Arg415Thr) in methionine synthase reductase (~4% global frequency). The T allele changes an arginine to threonine residue. Limited published evidence exists for independent clinical significance.

Allele T

OR —

p —

N 1,225

Preliminary work

European

Laraqui A et al. “Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and relation to risk of coronary artery disease.” Acta Cardiologica 61(1):51-61 (2006)

Allele T

OR —

p 1.2e-1

Candidate gene study

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ClinVar annotation

Benign★☆☆☆

6 submitters2 publications

Disorders of Intracellular Cobalamin Metabolism; Methylcobalamin deficiency type cblE (HMAE); not specified

rs2287780

Key Literature Trait Associations

Colorectal cancer

Hepatocellular carcinoma

Methionine Synthase Reductase Activity

ClinVar annotation

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