Association of RFC1 A80G and MTHFR C677T polymorphisms with Alzheimer's disease

Abstract We examined polymorphisms in reduced folate carrier gene ( RFC1 ) and methylenetetrahydrofolate reductase gene ( MTHFR ) for association with sporadic AD (SAD) in Chinese population. Significant associations of RFC1 A80G G allele and GG genotype with SAD ( p = 0.008, OR = 1.312, 95%CI = 1.072–1.605, and p = 0.042, OR = 1.383, 95%CI = 1.012–1.890) were found. Further stratification of total samples by APOE ε 4 carrier status, age/age at onset and gender revealed that RFC1 A80G G allele was an APOE ε 4-independent risk factor for late-onset AD, and it might increase the risk of AD in females. No significant associations of MTHFR C677T allele and genotype with AD were observed in total samples, but significant associations of T allele and TT genotype with AD ( p = 0.031, OR = 1.586, 95%CI = 1.042–2.414, and p = 0.028, OR = 2.250, 95%CI = 1.074–4.712) were identified in APOE ε 4 carrier subgroup, suggesting that MTHFR 677 T allele and APOE ε 4 allele may synergistically act to increase AD risk. No significant effect of RFC1 G80A and MTHFR C677T polymorphisms on plasma folate and homocysteine levels was detected.