Naslov
Glycomic and genetic biomarkers of posttraumatic stress disorder

Autori
Tudor, Lucija ; Nikolac Perković, Matea ; Nedić Erjavec, Gordana ; Švob Štrac, Dubravka ; Konjevod, Marcela ; Uzun, Suzana ; Kozumplik, Oliver ; Pivac, Nela

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
32. ECNP Kongres

Mjesto i datum
Kopenhagen, Danska, 07.09.2019. - 10.09.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
PTSD ; polymorphism, N-glycan ; biomarkers

Sažetak
Posttraumatic stress disorder (PTSD) can develop after experiencing or witnessing traumatic event(s). The lack of validated biomarkers and low remission rate, as well as frequent comorbidities such as depression, alcoholism, metabolic syndrome and cardiovascular diseases [1] are representing high socioeconomical burden. Risk factors involved in development and severity of PTSD are probably lying in a complex network of genetic, epigenetic and biological predesposition and psychiological, environmental factors as well as the character of the trauma itself. Protein glycosylation is the most common post- translational modification affecting more than 70% of plasma proteins. It can significantly alter biological role of the protein and signalling pathways by changing their physio- chemical properties. It was shown that glycosylation pattern drastically changes with aging, as well as in various diseases [2]. There is only one small study [3] that showed differences in N-glycome in patients with PTSD versus low stressed group, but these results lack the replication. Although there is no predefined pattern of sugar binding to the protein, there are several enzymes involved in this process that could contribute to the amount and type of glycosylation. Some of the single nucleotide polymorphisms (SNPs) were detected in genes encoding for those enzymes in a recent GWAS study [4] where one of the strongest hits were SNPs rs11621121, rs7953249, rs1257220 and rs3760776 located in fucosyltransferase-8, homeobox-A antisense RNA, alpha-1, 6- mannosylglycoprotein-6-beta-N- acetylglucosaminyltransferase-A and fucosyltransferase-3 gene regions, respectively. The aim of our study was to determine glycomic and genetic differences in patients with PTSD and controls. Discovery cohort consisted of 233 unrelated, Causasian, male war veterans with PTSD and healthy controls, while replication cohort involved 310 individuals. Genotyping of chosen SNPs (rs11621121, rs7953249, rs1257220, rs3760776) was done using real-time PCR. Plasma glycans were determined using ultra-high performance liquid chromatography that distinguished 39 N- glycan species. The differences in distribution of N-glycans between PTSD and controls, as well as between different genotypes was calculated using Student t-test and ANOVA, respectively, on values corrected for the effect of age and multiple testing. Differences in distribution of genotypes was calculated with chi-square test. There were total of 19 altered N-glycans in plasma of patients with PTSD in discovery cohort of which 6 of them replicated in the second one. Also, 3 out of 4 tested SNPs (rs11621121, rs7953249, rs1257220) were differentially distributed between PTSD and control samples. The effect of the genotypes on N-glycan distribution was calculated in subsets of samples divided by both cohort and diagnose. The most significant differences in N-glycome that were replicated in both cohorts were associated with rs3760776 genotype in control group where 6 of the N-glycans were differentially distributed depending on genotype. The results of other selected SNPs were more modest in both PTSD and control groups. Our study showed that changes in plasma protein glycosylation in PTSD are similar to changes seen in different inflammatory and pathophysiological states, as well as the potential role of genes involved in glycosylation process in the development of PTSD. This research was supported by the Croatian Science Foundation, project No. IP- 2014-09-4289.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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