The association of the polymorphisms in the FUT8-related locus 2 with the plasma glycosylation in post-traumatic stress disorder

Tudor, Lucija; Nedić Erjavec, Gordana; Nikolac Perković, Matea; Konjevod, Marcela; Uzun, Suzana; Kozumplik, Oliver; Mimica, Ninoslav; Lauc, Gordan; Švob Štrac, Dubravka; Pivac, Nela (2023) The association of the polymorphisms in the FUT8-related locus 2 with the plasma glycosylation in post-traumatic stress disorder. International Journal of Molecular Sciences, 24 (6). ISSN 1422-0067

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Official URL: https://www.mdpi.com/1422-0067/24/6/5706

Abstract

Molecular underpinnings of posttraumatic stress disorder (PTSD) are still unclear due to complex interactions of genetic, psychological, and environmental factors. Glycosylation is a common post-translational modification of proteins and different pathophysiological states, such as inflammation, autoimmune diseases, and mental disorders including PTSD, show altered N-glycome. Fucosyltransferase 8 (FUT8) is the enzyme that catalyzes the addition of core fucose on glycoproteins, and mutations in the FUT8 gene are associated with defects in glycosylation and functional abnormalities. This is the first study that investigated associations of plasma N-glycan levels with FUT8-related rs6573604, rs11621121, rs10483776, rs4073416 polymorphisms, and their haplotypes, in 541 PTSD patients and control participants. The results demonstrated that the rs6573604 T allele was more frequent in PTSD than in control participants. Significant associations of plasma N-glycan levels with PTSD and FUT8-related polymorphisms were observed. We also detected associations of rs11621121 and rs10483776 polymorphisms, and their haplotype, with plasma levels of specific N-glycan species in both the control and PTSD group. In carriers of different rs6573604 and rs4073416 genotypes and alleles, differences in plasma N-glycan levels were found only in the control group. These molecular findings suggest a possible regulatory role of FUT8-related polymorphisms in glycosylation, which alternations could partially explain the development and clinical manifestation of PTSD.

Item Type:

Article

Uncontrolled Keywords:

post-traumatic stress disorder; FUT8; FUT8-related polymorphisms; glycosylation; haplotype; N-glycans; plasma

Subjects:

BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Human Genetics, Genomics and Proteomics
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Neuroscience
BIOMEDICINE AND HEALTHCARE > Clinical Medical Sciences > Psychiatry

Divisions:

Division of Molecular Medicine

Projects: