Association analysis of CβS 844ins68 and MTHFD1 G1958A polymorphisms with Alzheimer’s disease in Chinese

Folate deficiency and elevated plasma homocysteine play important roles in pathogenesis of Alzheimer’s disease (AD). The aim of this study was to test the association of folate metabolism-related genes, cystathionine beta-synthase gene (CβS) and 5, 10-methylenetetrahydrofolate dehydrogenase gene (MTHFD1), with sporadic AD. The CβS 844ins68 polymorphism was determined by PCR and the MTHFD1 G1958A single nucleotide polymorphism (rs2236225) by PCR-RFLP. No significant difference of allele and genotype contributions of the CβS polymorphism between AD cases and controls was detected, before and after stratification by APOE ε4-carrying status, age/age at onset and genders. No significant difference of allele and genotype contributions of the MTHFD1 polymorphism between AD cases and controls was detected in total samples. When stratified by age/at onset age, we found that A allele and AA genotype frequencies in cases were higher than in controls and the differences were close to significant [A vs. G, P = 0.032, Odds ratio (OR) 1.642, 95% CI 1.040–2.591; AA + GA vs. GG, P = 0.068, OR 1.665, 95% CI 0.961–2.885; AA vs. GG, P = 0.059, OR 3.458, 95% CI 0.894–13.369] in <65 years groups, which suggested that the MTHFD1 G1958A A allele might be a weak risk factor for early onset AD although it needs further confirmation.