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

Abstract

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 (CbetaS) and 5, 10-methylenetetrahydrofolate dehydrogenase gene (MTHFD1), with sporadic AD. The CbetaS 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 CbetaS polymorphism between AD cases and controls was detected, before and after stratification by APOE epsilon4-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.

Metabolic profiling of a transgenic Caenorhabditis elegans Alzheimer model

“…Polymorphisms in cystathionine beta synthase (CBS), catalyzing the conversion of homocysteine to cystathionine, are well-known risk factors for AD (Perluigi and Butterfield 2012). These gene polymorphisms are known to decrease CBS activity and cause a high concentration of homocysteine and a low concentration of cystathionine (Bi et al 2010), in line with our observations in C. elegans .…”

MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian population

“…The presence of MTHFD1 rs2236225 polymorphism has been described as maternal and offspring risk factor for several conditions, including neural tube defects (Etheredge et al, ), severe placental abruption and miscarriage (Parle‐McDermott et al, , b), intrauterine growth restriction (Furness et al, ), and congenital heart defects in children (Christensen et al, ). Furthermore, rs2236225 was associated with decreased risk for lung cancer (Liu et al, ), but not in cancers of prostate (Collin et al, ), cervix (Mostowska et al, ), and ovaries (Pawlik et al, ), and the A variant allele was also suggested as a risk factor for early onset Alzheimer's disease (Bi et al, ). There are few studies describing the association of rs2236225 polymorphism and maternal risk for NSCL/P, and the results are unclear.…”

A hybrid of thiazolidinone with the hydroxamate scaffold for developing novel histone deacetylase inhibitors with antitumor activities

“…Condensation of this amine intermediate 15 with succinic or pimelic acid anhydride in 1,4-dioxane and subsequent esterification afforded ester compounds, and then the ester groups were treated with NH 2 OH•HCl in methanol to obtain compounds 10a-b. 42 Compounds 11a-b were prepared by following the methods described in Scheme 2. The starting material 17 was synthesized in a similar manner of step 1 of Scheme 1, then the ester group was hydrolyzed under basic conditions to yield acid analogue 18, which was coupled with amino acid esters (n = 3 or 5) and the target compounds were achieved by transforming the ester to the hydroxamate group.…”