rs1801198

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). Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Environmental influence on the worldwide prevalence of a 776C->G variant in the transcobalamin gene (TCN2). Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts. Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate. Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer. Gene-gene interactions in the folate metabolic pathway and the risk of conotruncal heart defects. Polymorphic variants of genes involved in homocysteine metabolism in celiac disease. Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population.

G;G

see discussion at rs1801198