Genetics

This post covers Grigorian and colleagues' 2012 review in Seminars in Immunopathology, arguing that genetic variants in IL7RA, IL2RA, MGAT1 and CTLA-4 together with vitamin D and nutrient supply converge on Golgi N-glycan branching in MS. It covers the enzyme kinetics that make the pathway metabolically sensitive, the epistasis data showing the MGAT1 haplotype reversing direction depending on other alleles, what that implies for point-association studies, the swainsonine blocking experiment that puts branching on the causal path from vitamin D, the case for N-acetylglucosamine over glucosamine, and the limits of reading a 2012 therapeutic recommendation today.