Deregulation of folate and vitamin B12 (VB12) metabolism contributes to the risk of congenital heart defects (CHDs). Transcobalamin (TCN2) is essential for transporting VB12 from blood to cells as TCN2-bound VB12 (holo-TC) is the only form for somatic cellular uptake. In this study, we performed an association study between common polymorphisms in 46 one carbon metabolism genes and CHD in 412 CHDs and 213 controls. Only two significant association signals in coding regions were identified: FTCD c. 1470C> T & TCN2 c. 230A> T. The only missense mutation, TCN2 c. 230A> T, was further validated in 412 CHDs and 1177 controls. TCN2 c. 230T is significantly associated with reduced CHD risk in North Chinese (odds ratio = 0.67, P = 4.62e-05), compared with the 230A allele. Interestingly, the mean level of plasma holo-TC in women with the TA genotype was 1.77-fold higher than that in women with the AA genotype. Further analysis suggested that c. 230A> T enhanced the cellular uptake of holo-TC via the LRP2 receptor. Our results determined that a functional polymorphism in TCN2 contributes to the prevalence of CHDs. TCN2 c. 230A> T is significantly associated with a reduced CHD risk, likely due to TCN2 c. 230T improving the interaction between holo-TC and its LRP2 receptor.

Creating hierarchical porosity in MOFs has attracted significant interest due to their immense potential in a wide range of applications from materials to life science. Herein, we report a unique methodology of combining perturbation assisted nanofusion (PNF) with microwave (MW) stimuli to generate wide additional pores from (5-18) nm in the prototype MOF, NiMOF-74. An optimized combination of microwave exposure, perturbation in form of stirring, and solvent effect induces additional mesoscale porosity by fusion of MOF nanoparticles. The effect of microwave is realized by varying reaction time and medium using a range of solvents having different dielectric constant (DMSO, DMF, DMA, acetone, EA, and THF). Introducing this method, for the first time, we are able to generate a wide scale mesopore by fusion of nanoscale microporous MOF within a short reaction time by vigorous stirring, without using any template. This additional mesopore, thus generated, has been exploited by encapsulating 4.6 mu mol.g(-1) of large biomolecule Vitamin B-12 (VB12).