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- W2563842212 abstract "Glycans constitute the most abundant and diverse form of the post-translational modifications. While genesunequivocally determine the structure of each polypeptide, there is no genetic template for the glycan part.Instead, hundreds of genes and their products interact in the very complex pathway of glycan biosynthesiswhich is further complicated by environmental influences. Therefore, the aim of this thesis was todetermine the extent to which individual differences in immunoglobulin G and total plasma proteinsglycosylation patterns reflect genetic versus environmental influences. A twin study design was used andstudy subjects were twins enrolled in the TwinsUK registry, a national register of adult twins. More than4500 samples were analyzed by HILIC-UPLC (Hydrophilic Interaction Ultra Performance LiquidChromatography). A high contribution of the genetic component to N-glycome composition was found.Variation in levels of 51 of the 76 IgG glycan traits studied was at least 50% heritable and only a smallproportion of N-glycan traits had a low genetic contribution. Heritability of plasma N-glycome was alsohigh, with half of the plasma glycan traits being at least 50% heritable. Further, epigenome-wide association(EWA) analysis showed that methylation levels at some genes are also implicated in glycome composition,both in those with high heritability and those with a lower genetic contribution. The study to investigate thepotential role of glycosylation in kidney function was also conducted. Fourteen IgG glycan traits wereassociated with renal function in discovery population and remained significant after validation in anindependent subset of monozygotic twins discordant for renal disease, reflecting difference ingalactosylation, sialylation, and level of bisecting N-acetylglucosamine. Using the weighted correlationnetwork analysis (WGCNA) for IgG glycan traits, a correlation between low back pain (LBP) and glycanmodules was established. There was a weak positive correlation between pain phenotypes and proantibody-dependent cell-mediated cytotoxicity (ADCC) WGCNA glycan modules (high bisecting Nacetylglucosamineand low core fucose) and a weak negative correlation between pain phenotypes andanti-ADCC module (high core fucose, no bisecting N-acetylglucosamine). This suggests that glycans arepromising candidates for biomarkers in many different diseases." @default.
- W2563842212 created "2017-01-06" @default.
- W2563842212 creator A5051077634 @default.
- W2563842212 date "2016-07-12" @default.
- W2563842212 modified "2023-09-24" @default.
- W2563842212 title "Influence of genetic and environmental factors on N-glycosylation of immunoglobulin G and total plasma proteins determined by twin study" @default.
- W2563842212 hasPublicationYear "2016" @default.
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