|(G;G)||2||Some increase in peripheral neuropathy risk in older adults taking folate|
rs1801198, also known as c.776G>C, p.Arg259Pro and R259P, is a common variant in the TCN2 gene on chromosome 22. Note that in older (pre-2003) literature this variant was known as c.775G>C.
A relatively small study published in 2016 of ~170 adults over 60 years of age concluded that rs1801198(G;G) individuals have significantly (~3x) higher risk of peripheral neuropathy, even with a normal vitamin B-12 status, and especially if their folate intake is >800 micrograms/day (i.e. 2 times the Recommended Dietary Allowance, with a reported OR of 6.9, CI:1.31- 36.36). In other words, excess folate (including folic acid) is more likely to lead to a burning, tingling or numbness in the hands and feets of older adults who happen to be rs1801198(G;G) genotypes. There was no difference in neuropathy risk between genotypes when folate intake was less than 800 micrograms per day; overall, the odds of neuropathy were 3-fold higher for GG genotypes than for CC genotypes (OR 3.33, CI: 1.15-9.64).[PMID 27733392]
|Disease Association||Defects in TCN2 are the cause of transcobalamin II deficiency (MIM:275350). This results in various forms of anemia.|
[PMID 21429654] Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility
[PMID 22794911] A candidate gene study of one-carbon metabolism pathway genes and colorectal cancer risk
|Disease||TCN2 POLYMORPHISM Transcobalamin II deficiency not specified|
|CLNDBN||TCN2 POLYMORPHISM Transcobalamin II deficiency not specified|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
|CLNACC||RCV000000117.2, RCV000374451.1, RCV000454394.1,|
[PMID 17035141] Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions.
[PMID 17220211] Environmental influence on the worldwide prevalence of a 776C->G variant in the transcobalamin gene (TCN2).
[PMID 18203168] Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts.
[PMID 18661527] Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.
[PMID 19936946] Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer.
[PMID 20111745] Gene-gene interactions in the folate metabolic pathway and the risk of conotruncal heart defects.
[PMID 21688148] Polymorphic variants of genes involved in homocysteine metabolism in celiac disease.
[PMID 22183302] Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population.
|qualified_impact||Insufficiently evaluated not reviewed|
[PMID 23089108] Idiopathic pulmonary fibrosis and polymorphisms of the folate pathway genes
[PMID 26540672] Non-syndromic cleft lip with or without cleft palate in Asian populations: Association analysis on three gene polymorphisms of the folate pathway