CUBN was the only other gene with more than one selleckchem Calcitriol SNP found in the ten most strongly associated signals. CUBN rs7070148 and CUBN rs2273737 were both sig nificant for association with maternal risk in a continu ous model of logistic regression. There are three other highly significant SNPs in CUBN. Two other SNPs in the same haplotype block with CUBN rs7070148 and CUBN rs2273737 also showed an association with maternal effects. A third SNP, CUBN rs11591606, is out side this block and is associated with maternal risk in a dominant model of logistic regression. Correction for multiple testing was performed for three of the twelve tests of association. No adjusted p value was found to remain significant, and no further correction was performed. Discussion This study represents a new scale of evaluation of gen etic contribution to NTD risk.
Common variants in 82 biologically plausible candidate genes were tested for as sociation with NTDs in a large Irish population. Seven teen variants in nine genes account for the ten most significant associations Inhibitors,Modulators,Libraries observed. CDKN2A, GART, DNMT3A, MTHFD1 and T contained a sin gle SNP among the ten lowest p values observed for all tests. In contrast, MFTC, ADA, PEMT, Inhibitors,Modulators,Libraries and CUBN each contained more than one such SNP. This seems to be due to strong LD relationships between the associated SNPs. The only exception is in ADA, which shows evi dence of two strong, unrelated association signals. ADA converts adenosine to in osine by removal of an amino group. Deficiency in this enzyme causes severe combined immunodeficiency dis ease, which is characterized by compromise of both T cells and B cells.
Interestingly, ADA activity was significantly elevated in a study of 68 pregnant women carrying Inhibitors,Modulators,Libraries a fetus with a central nervous system malforma tion. of these women, 17 had a spina bifida preg nancy. Consistent with Inhibitors,Modulators,Libraries this, six unrelated, noncoding ADA SNPs were found in the current study to be associated with maternal risk of carrying an NTD pregnancy. Genetic variation in ADA may contribute to maternal risk of NTDs. In addition, this gene was the only one to exhibit two inde pendent association signals among the top ten signals observed. This may indicate that there is more than one allele associated with risk or the same allele has recurred on more than one haplotype.
ADA rs6031682 shows evi dence of case effects as well as maternal effects in log linear analyses of a dominant model, and it is clearly independent of the other signifi cant ADA SNPs. It would be of interest to test the associated ADA SNPs in an independent study, espe cially since the scale of Inhibitors,Modulators,Libraries correction would be much smal ler in a focused study. selleck products PEMT plays a role in choline metabolism. It converts phos phatidylethanolamine to phosphatidylcholine in the liver. phosphatidylcholine is a major component of cell mem branes. This role for choline can compete with its role as a methyl donor.